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2-AZETIDINONE, 1-(4-FLUOROPHENYL)-3-[(3S)-3-(4-FLUOROPHENYL)-3-HYDROXYPROPYL]-4-[4-(PHENYLMETHOXY)PHENYL]-, (3R,4S)is a complex organic compound with a unique molecular structure. It is characterized by its off-white solid appearance and is primarily used as a protected form of Ezetimibe in the synthesis of related derivatives.

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    Cas No: 163222-32-0

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  • (3R,4S)-1-(4-Fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-phenylmethoxy)-phenyl]-2-azetidinone

    Cas No: 163222-32-0

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    1. Product Name: 2-AZETIDINONE, 1-(4-FLUOROPHENYL)-3-[(3S)-3-(4-FLUOROPHENYL)-3-HYDROXYPROPYL]-4-[4-(PHENYLMETHOXY)PHENYL]-, (3R,4S)-
    2. Synonyms: 2-AZETIDINONE, 1-(4-FLUOROPHENYL)-3-[(3S)-3-(4-FLUOROPHENYL)-3-HYDROXYPROPYL]-4-[4-(PHENYLMETHOXY)PHENYL]-, (3R,4S)-;1-(4-FLUOROPHENYL)-3-[(3S)-3-(4-FLUOROPHENYL)-3-HYDROXYPROPYL]-4-[4-(PHENYLMETHOXY)PHENYL]-, (3R,4S)-2-AZETIDINONE;1-(4-Fluorophenyl)-3-[(3s)-3-(4-Fluorophenyl)-3-Hydroxypropyl]-4-[4-(Phenylmethoxy)Phenyl-(3r,4s)-2-Azetidinone;1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-[4-phenylmethoxy]phenyl]-(3R,4S)-2-azetidinone (intermediate of ezetimibe);(3R,4S)-1-(4-Fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-[4-(phenylmethoxy)phenyl]-2-azetidinone;E7:synthesis of trans-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-hydroxypropyl-(4-benzyloxyphenyl)]-2-azetidinone;4’-O-Benzyloxy Ezetimibe;(3R,4S)-4-[(4-Benzyloxy)phenyl]-1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-2-azetidinone
    3. CAS NO:163222-32-0
    4. Molecular Formula: C31H27F2NO3
    5. Molecular Weight: 499.55
    6. EINECS: N/A
    7. Product Categories: (intermediate of ezetimibe);Ezetimibe intermediates;Aromatics;Chiral Reagents;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals
    8. Mol File: 163222-32-0.mol
  • Chemical Properties

    1. Melting Point: N/A
    2. Boiling Point: 706.462 °C at 760 mmHg
    3. Flash Point: 381.055 °C
    4. Appearance: Off-white solid
    5. Density: 1.270
    6. Vapor Pressure: 0mmHg at 25°C
    7. Refractive Index: 1.617
    8. Storage Temp.: Sealed in dry,Room Temperature
    9. Solubility: DMSO (Slightly), Methanol (Slightly, Heated)
    10. PKA: 14.15±0.20(Predicted)
    11. CAS DataBase Reference: 2-AZETIDINONE, 1-(4-FLUOROPHENYL)-3-[(3S)-3-(4-FLUOROPHENYL)-3-HYDROXYPROPYL]-4-[4-(PHENYLMETHOXY)PHENYL]-, (3R,4S)-(CAS DataBase Reference)
    12. NIST Chemistry Reference: 2-AZETIDINONE, 1-(4-FLUOROPHENYL)-3-[(3S)-3-(4-FLUOROPHENYL)-3-HYDROXYPROPYL]-4-[4-(PHENYLMETHOXY)PHENYL]-, (3R,4S)-(163222-32-0)
    13. EPA Substance Registry System: 2-AZETIDINONE, 1-(4-FLUOROPHENYL)-3-[(3S)-3-(4-FLUOROPHENYL)-3-HYDROXYPROPYL]-4-[4-(PHENYLMETHOXY)PHENYL]-, (3R,4S)-(163222-32-0)
  • Safety Data

    1. Hazard Codes: N/A
    2. Statements: N/A
    3. Safety Statements: N/A
    4. WGK Germany:
    5. RTECS:
    6. HazardClass: N/A
    7. PackingGroup: N/A
    8. Hazardous Substances Data: 163222-32-0(Hazardous Substances Data)

163222-32-0 Usage

Uses

Used in Pharmaceutical Industry:
2-AZETIDINONE, 1-(4-FLUOROPHENYL)-3-[(3S)-3-(4-FLUOROPHENYL)-3-HYDROXYPROPYL]-4-[4-(PHENYLMETHOXY)PHENYL]-, (3R,4S)is used as a protected form of Ezetimibe for the synthesis of related derivatives. This application is significant in the development of new drugs and therapies, as it allows for the creation of modified versions of Ezetimibe with potentially improved properties or targeted effects.
Chemical Properties:
The compound is an off-white solid, which indicates its stability and suitability for use in various chemical reactions and processes. Its specific properties, such as solubility and reactivity, can be further explored and optimized for specific applications in the pharmaceutical industry.

Check Digit Verification of cas no

The CAS Registry Mumber 163222-32-0 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,6,3,2,2 and 2 respectively; the second part has 2 digits, 3 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 163222-32:
(8*1)+(7*6)+(6*3)+(5*2)+(4*2)+(3*2)+(2*3)+(1*2)=100
100 % 10 = 0
So 163222-32-0 is a valid CAS Registry Number.
InChI:InChI=1/C31H27F2NO3/c32-24-10-6-22(7-11-24)29(35)19-18-28-30(34(31(28)36)26-14-12-25(33)13-15-26)23-8-16-27(17-9-23)37-20-21-4-2-1-3-5-21/h1-17,28-30,35H,18-20H2/t28-,29+,30-/m1/s1

163222-32-0SDS

SAFETY DATA SHEETS

According to Globally Harmonized System of Classification and Labelling of Chemicals (GHS) - Sixth revised edition

Version: 1.0

Creation Date: Aug 18, 2017

Revision Date: Aug 18, 2017

1.Identification

1.1 GHS Product identifier

Product name 4'-O-Benzyloxy Ezetimibe

1.2 Other means of identification

Product number -
Other names 2-AZETIDINONE, 1-(4-FLUOROPHENYL)-3-[(3S)-3-(4-FLUOROPHENYL)-3-HYDROXYPROPYL]-4-[4-(PHENYLMETHOXY)PHENYL]-, (3R,4S)-

1.3 Recommended use of the chemical and restrictions on use

Identified uses For industry use only.
Uses advised against no data available

1.4 Supplier's details

1.5 Emergency phone number

Emergency phone number -
Service hours Monday to Friday, 9am-5pm (Standard time zone: UTC/GMT +8 hours).

More Details:163222-32-0 SDS

163222-32-0Synthetic route

(3R,4S)-4-[4-(benzyloxy)phenyl]-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-oxopropyl]azetidin-2-one
190595-65-4

(3R,4S)-4-[4-(benzyloxy)phenyl]-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-oxopropyl]azetidin-2-one

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
With formic acid; [(S,S)-teth-TsDpen RuCl]; triethylamine In ethylbenzene at 35 - 40℃; for 24h; Inert atmosphere;99.8%
With methanesulfonic acid; dimethylsulfide borane complex; (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole In tetrahydrofuran; methyl tertiarybutylether; toluene at -25 - -20℃; for 2.5 - 3.5h; Product distribution / selectivity;98.04%
With methanesulfonic acid; dimethylsulfide borane complex; (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole In tetrahydrofuran; toluene at -25 - -20℃; for 2.5 - 3.5h; Product distribution / selectivity;98.6%
benzyl bromide
100-39-0

benzyl bromide

ezetemibe
163222-33-1

ezetemibe

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
With caesium carbonate In N,N-dimethyl-formamide at 20℃; for 3h;99%
(3R,4S)-4-[4-(benzyloxy)phenyl]-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-oxopropyl]azetidin-2-one
190595-65-4

(3R,4S)-4-[4-(benzyloxy)phenyl]-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-oxopropyl]azetidin-2-one

A

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

B

(3R,4S,3'R)-1-(4-fluorophenyl)-4-(4-hydroxyphenyl)-3-[3'-(4-fluorophenyl)-3'-hydroxy-propyl]-azetidin-2-one
163380-15-2

(3R,4S,3'R)-1-(4-fluorophenyl)-4-(4-hydroxyphenyl)-3-[3'-(4-fluorophenyl)-3'-hydroxy-propyl]-azetidin-2-one

Conditions
ConditionsYield
With dimethylsulfide borane complex In tetrahydrofuran at 22℃; for 3h;A 0.141 g
B n/a
With dimethylsulfide borane complex In tetrahydrofuran at 22℃; for 3h;
Stage #1: (3R,4S)-4-[4-(benzyloxy)phenyl]-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-oxopropyl]azetidin-2-one With sodium tetrahydroborate; chloro-trimethyl-silane; (R)-α,α-diphenylprolinol In tetrahydrofuran at 19 - 22℃; for 2.78333h; Heating / reflux;
Stage #2: With hydrogenchloride; water In tetrahydrofuran; toluene at 2℃; for 0.5h; Product distribution / selectivity;
A n/a
B n/a
With 1,1,1,3',3',3'-hexafluoro-propanol; C32H39BrMnN2O2P; potassium tert-butylate; hydrogen In methanol at 20℃; under 22502.3 Torr; for 16h; Glovebox; Autoclave; Overall yield = 99 %; enantioselective reaction;A n/a
B n/a
With C32H39BrMnN2O2P; potassium tert-butylate; hydrogen In methanol at 20℃; under 22502.3 Torr; for 16h; Glovebox; Autoclave; Optical yield = 85 percent ee; enantioselective reaction;
4-benzyloxybenzylidene-N-(4-fluoro)phenylanisidine
70627-52-0

4-benzyloxybenzylidene-N-(4-fluoro)phenylanisidine

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 6 steps
1: 64 percent / LDA; DMPU; LiCl / dimethylformamide; tetrahydrofuran / 18 h / -30 - -25 °C
2: 90 percent / NaIO4 / acetonitrile; H2O / 2 h / 20 °C
3: BF3 etherate / toluene / 0.08 h / -30 °C
4: 99 g / p-toluenesulfonic acid monohydrate; molecular sieves / toluene / 4 h / 40 - 50 °C
5: 71 percent / (PPh3)3RhCl; hydrogen / CH2Cl2 / 18 h / 3102.89 Torr
6: 70 percent / CBS; BH3-Me2S / toluene; CH2Cl2 / 2 h / -20 °C
View Scheme
Multi-step reaction with 4 steps
1: N-ethyl-N,N-diisopropylamine; titanium(IV) isopropylate; titanium tetrachloride / dichloromethane / 3 h / -5 °C
2: N,O-Bis(trimethylsilyl)acetamide; tetrabutyl ammonium fluoride / toluene / 48 h / Reflux
3: formic acid / dichloromethane / 12 h / Reflux
4: dimethyl sulfide borane / dichloromethane; toluene; tetrahydrofuran / 12 h / 15 °C
View Scheme
Multi-step reaction with 2 steps
1: N,O-bis-(trimethylsilyl)-acetamide; tetrabutyl ammonium fluoride / toluene / 60 °C
2: dimethylsulfide borane complex / dichloromethane; toluene / 3 h / -5 - 0 °C / Inert atmosphere
View Scheme
(2S,3S)-2-(4-(benzyloxy)phenyl)-1-(4-fluorophenyl)-4-oxazetidine-3-carbaldehyde
221349-58-2

(2S,3S)-2-(4-(benzyloxy)phenyl)-1-(4-fluorophenyl)-4-oxazetidine-3-carbaldehyde

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 4 steps
1: BF3 etherate / toluene / 0.08 h / -30 °C
2: 99 g / p-toluenesulfonic acid monohydrate; molecular sieves / toluene / 4 h / 40 - 50 °C
3: 71 percent / (PPh3)3RhCl; hydrogen / CH2Cl2 / 18 h / 3102.89 Torr
4: 70 percent / CBS; BH3-Me2S / toluene; CH2Cl2 / 2 h / -20 °C
View Scheme
(3S,4S)-4-(4-Benzyloxy-phenyl)-3-((S)-1,2-dihydroxy-ethyl)-1-(4-fluoro-phenyl)-azetidin-2-one
221349-56-0

(3S,4S)-4-(4-Benzyloxy-phenyl)-3-((S)-1,2-dihydroxy-ethyl)-1-(4-fluoro-phenyl)-azetidin-2-one

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 5 steps
1: 90 percent / NaIO4 / acetonitrile; H2O / 2 h / 20 °C
2: BF3 etherate / toluene / 0.08 h / -30 °C
3: 99 g / p-toluenesulfonic acid monohydrate; molecular sieves / toluene / 4 h / 40 - 50 °C
4: 71 percent / (PPh3)3RhCl; hydrogen / CH2Cl2 / 18 h / 3102.89 Torr
5: 70 percent / CBS; BH3-Me2S / toluene; CH2Cl2 / 2 h / -20 °C
View Scheme
lithium; 1-(4-fluoro-phenyl)-ethenolate

lithium; 1-(4-fluoro-phenyl)-ethenolate

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 4 steps
1: BF3 etherate / toluene / 0.08 h / -30 °C
2: 99 g / p-toluenesulfonic acid monohydrate; molecular sieves / toluene / 4 h / 40 - 50 °C
3: 71 percent / (PPh3)3RhCl; hydrogen / CH2Cl2 / 18 h / 3102.89 Torr
4: 70 percent / CBS; BH3-Me2S / toluene; CH2Cl2 / 2 h / -20 °C
View Scheme
(3R,4S)-4-(4-Benzyloxy-phenyl)-1-(4-fluoro-phenyl)-3-[(E)-3-(4-fluoro-phenyl)-3-oxo-propenyl]-azetidin-2-one
221349-60-6

(3R,4S)-4-(4-Benzyloxy-phenyl)-1-(4-fluoro-phenyl)-3-[(E)-3-(4-fluoro-phenyl)-3-oxo-propenyl]-azetidin-2-one

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: 71 percent / (PPh3)3RhCl; hydrogen / CH2Cl2 / 18 h / 3102.89 Torr
2: 70 percent / CBS; BH3-Me2S / toluene; CH2Cl2 / 2 h / -20 °C
View Scheme
(3S,4S)-4-(4-Benzyloxy-phenyl)-1-(4-fluoro-phenyl)-3-[3-(4-fluoro-phenyl)-1-hydroxy-3-oxo-propyl]-azetidin-2-one
231301-00-1

(3S,4S)-4-(4-Benzyloxy-phenyl)-1-(4-fluoro-phenyl)-3-[3-(4-fluoro-phenyl)-1-hydroxy-3-oxo-propyl]-azetidin-2-one

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 3 steps
1: 99 g / p-toluenesulfonic acid monohydrate; molecular sieves / toluene / 4 h / 40 - 50 °C
2: 71 percent / (PPh3)3RhCl; hydrogen / CH2Cl2 / 18 h / 3102.89 Torr
3: 70 percent / CBS; BH3-Me2S / toluene; CH2Cl2 / 2 h / -20 °C
View Scheme
(Z)-1-(4-(benzyloxy)phenyl)-N-(4-fluorophenyl)methaneimine
219653-96-0

(Z)-1-(4-(benzyloxy)phenyl)-N-(4-fluorophenyl)methaneimine

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 5 steps
1: (nBu)3N / heptane; toluene / 80 - 90 °C
2: LiOH*H2O / methanol / 2 h
3: oxalyl chloride / CH2Cl2 / 16 h / 22 °C
4: (Ph3P)4Pd / tetrahydrofuran / 1 h / 10 °C
5: BH3*Me2S / tetrahydrofuran / 3 h / 22 °C
View Scheme
(3R,4S)-1-(4-fluorophenyl)-3-(3-hydroxy-3-oxopropyl)-4-(4-benzyloxyphenyl)-2-azetidinone
204589-82-2

(3R,4S)-1-(4-fluorophenyl)-3-(3-hydroxy-3-oxopropyl)-4-(4-benzyloxyphenyl)-2-azetidinone

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 3 steps
1: oxalyl chloride / CH2Cl2 / 16 h / 22 °C
2: (Ph3P)4Pd / tetrahydrofuran / 1 h / 10 °C
3: BH3*Me2S / tetrahydrofuran / 3 h / 22 °C
View Scheme
3-((3R,4S)-1-(4-fluorophenyl)-2-oxo-4-(4-(benzyloxy)phenyl)azetidin-3-yl)propionic acid chloride
204589-84-4

3-((3R,4S)-1-(4-fluorophenyl)-2-oxo-4-(4-(benzyloxy)phenyl)azetidin-3-yl)propionic acid chloride

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: (Ph3P)4Pd / tetrahydrofuran / 1 h / 10 °C
2: BH3*Me2S / tetrahydrofuran / 3 h / 22 °C
View Scheme
methyl 3-((2S,3R)-2-(4-(benzyloxy)phenyl)-1-(4-fluorophenyl)-4-oxoazetidin-3-yl)propanoate
204589-80-0

methyl 3-((2S,3R)-2-(4-(benzyloxy)phenyl)-1-(4-fluorophenyl)-4-oxoazetidin-3-yl)propanoate

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 4 steps
1: LiOH*H2O / methanol / 2 h
2: oxalyl chloride / CH2Cl2 / 16 h / 22 °C
3: (Ph3P)4Pd / tetrahydrofuran / 1 h / 10 °C
4: BH3*Me2S / tetrahydrofuran / 3 h / 22 °C
View Scheme
Multi-step reaction with 3 steps
1.1: diethyl aluminiumcholoride / toluene / -12 - 20 °C / Inert atmosphere
2.1: magnesium / tetrahydrofuran / 1 h / 40 - 50 °C / Inert atmosphere
2.2: 1 h / -5 - 0 °C
3.1: [(S,S)-teth-TsDpen RuCl]; triethylamine; formic acid / ethylbenzene / 24 h / 35 - 40 °C / Inert atmosphere
View Scheme
[14C]-Sch 57871
191330-56-0

[14C]-Sch 57871

(3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole
112022-83-0

(3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Stage #1: [14C]-Sch 57871; (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole In tetrahydrofuran at -20℃; for 0.0833333h;
Stage #2: With dimethylsulfide borane complex In tetrahydrofuran at -20℃; for 1.5h;
1-(4-fluorophenyl)-4(S)-(4-hydroxyphenyl)-3(R)-(3-oxo-3-phenylpropyl)-2-azetidinone
163222-31-9

1-(4-fluorophenyl)-4(S)-(4-hydroxyphenyl)-3(R)-(3-oxo-3-phenylpropyl)-2-azetidinone

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
With dimethylsulfide borane complex; (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole In tetrahydrofuran at -20℃; for 1.5h;
methanol
67-56-1

methanol

(3R,4S)-4-[4-(benzyloxy)phenyl]-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-oxopropyl]azetidin-2-one
190595-65-4

(3R,4S)-4-[4-(benzyloxy)phenyl]-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-oxopropyl]azetidin-2-one

(3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole
112022-83-0

(3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
With hydrogenchloride In tetrahydrofuran
1-Bromo-4-fluorobenzene
460-00-4

1-Bromo-4-fluorobenzene

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1.1: magnesium; Bis<2-(N,N-dimethylamino)aethyl>aether / 0.5 h / 0 °C
2.1: (R)-1,1'-Bi-2-naphthol / titanium(IV) isopropylate / diethyl ether; tetrahydrofuran / 1.5 h / 0 - 25 °C
2.2: -20 - 25 °C
2.3: 0 °C
View Scheme
Multi-step reaction with 2 steps
1.1: magnesium / tetrahydrofuran / 1 h / 40 - 50 °C / Inert atmosphere
1.2: 1 h / -5 - 0 °C
2.1: [(S,S)-teth-TsDpen RuCl]; triethylamine; formic acid / ethylbenzene / 24 h / 35 - 40 °C / Inert atmosphere
View Scheme
3-[(2S,3R)-2-(4-(benzyloxy)phenyl)-1-(4-fluorophenyl)-4-oxoazetidin-3-yl]propanal
1412967-16-8

3-[(2S,3R)-2-(4-(benzyloxy)phenyl)-1-(4-fluorophenyl)-4-oxoazetidin-3-yl]propanal

4-flourophenylmagnesium bromide
352-13-6

4-flourophenylmagnesium bromide

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Stage #1: 4-flourophenylmagnesium bromide With (R)-1,1'-Bi-2-naphthol; titanium(IV) isopropylate In tetrahydrofuran; diethyl ether at 0 - 25℃; for 1.5h;
Stage #2: 3-[(2S,3R)-2-(4-(benzyloxy)phenyl)-1-(4-fluorophenyl)-4-oxoazetidin-3-yl]propanal In tetrahydrofuran; diethyl ether at -20 - 25℃;
Stage #3: With hydrogenchloride; water In tetrahydrofuran; diethyl ether at 0℃;
(3R,4S)-4-(4-(benzyloxy)phenyl)-1-(4-fluorophenyl)-3-(3-hydroxypropyl)azetidin-2-one
1412967-14-6

(3R,4S)-4-(4-(benzyloxy)phenyl)-1-(4-fluorophenyl)-3-(3-hydroxypropyl)azetidin-2-one

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1.1: sodium hydrogencarbonate; sodium hypochlorite; potassium bromide; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical / Difluoromethane / 25 °C / Cooling with ice
2.1: (R)-1,1'-Bi-2-naphthol / titanium(IV) isopropylate / diethyl ether; tetrahydrofuran / 1.5 h / 0 - 25 °C
2.2: -20 - 25 °C
2.3: 0 °C
View Scheme
(1'R,6R)-3-[(4-benzyloxyphenyl)-(4-fluorophenylamino)-methyl]-6-(4-fluorophenyl)-5,6-dihydro-2H-pyran-2-one
1416263-33-6

(1'R,6R)-3-[(4-benzyloxyphenyl)-(4-fluorophenylamino)-methyl]-6-(4-fluorophenyl)-5,6-dihydro-2H-pyran-2-one

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 3 steps
1: lithium hydroxide / tetrahydrofuran; water / 18 h
2: triphenylphosphine; di-isopropyl azodicarboxylate / 3 h / 0 °C
3: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
(1'S,3R,6S)-3-[(4-benzyloxyphenyl)-(4-fluorophenylamino)-methyl]-6-(4-fluorophenyl)-tetrahydro-2H-pyran-2-one
1416263-36-9

(1'S,3R,6S)-3-[(4-benzyloxyphenyl)-(4-fluorophenylamino)-methyl]-6-(4-fluorophenyl)-tetrahydro-2H-pyran-2-one

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
With tert-butylmagnesium chloride In diethyl ether at 0℃; for 2h;
(3S,3aS,6S,7aS)-3-(4-(benzyloxy)phenyl)-2,6-bis(4-fluorophenyl)tetrahydro-2H-pyrano[3,4-d]isoxazol-4(6H)-one
1416263-37-0

(3S,3aS,6S,7aS)-3-(4-(benzyloxy)phenyl)-2,6-bis(4-fluorophenyl)tetrahydro-2H-pyrano[3,4-d]isoxazol-4(6H)-one

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 4 steps
1: potassium iodide / acetonitrile; water / 0.58 h / 20 °C
2: Burgess Reagent / toluene / 18 h / 90 °C
3: platinum(IV) oxide; hydrogen / toluene / 20 °C / 750.08 Torr
4: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
(R)-2,3-dihydro-2-(4-fluorophenyl)-4H-pyran-4-one

(R)-2,3-dihydro-2-(4-fluorophenyl)-4H-pyran-4-one

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 10 steps
1: cerium(III) chloride heptahydrate; sodium tetrahydroborate / dichloromethane; methanol / 0.5 h / -20 °C
2: dihydrogen peroxide; molybdenum(VI) oxide / acetonitrile / 24 h
3: pyridine; acetic anhydride / dichloromethane / 2 h / 20 °C
4: toluene / 72 h / Reflux
5: lithium hydroxide monohydrate / tetrahydrofuran; water / 18 h
6: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran / 3 h / 0 °C
7: potassium iodide / acetonitrile; water / 0.58 h / 20 °C
8: Burgess Reagent / toluene / 18 h / 90 °C
9: platinum(IV) oxide; hydrogen / toluene / 20 °C / 750.08 Torr
10: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
Multi-step reaction with 10 steps
1: cerium(III) chloride heptahydrate; sodium tetrahydroborate / dichloromethane; methanol / 0.5 h / -20 °C
2: dihydrogen peroxide; molybdenum(VI) oxide / acetonitrile / 24 h
3: pyridine; acetic anhydride / dichloromethane / 2 h / 20 °C
4: scandium tris(trifluoromethanesulfonate) / toluene / 72 h / 30 °C / Molecular sieve
5: lithium hydroxide monohydrate / tetrahydrofuran; water / 18 h
6: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran / 3 h / 0 °C
7: potassium iodide / acetonitrile; water / 0.58 h / 20 °C
8: Burgess Reagent / toluene / 18 h / 90 °C
9: platinum(IV) oxide; hydrogen / toluene / 20 °C / 750.08 Torr
10: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
Multi-step reaction with 9 steps
1.1: cerium(III) chloride heptahydrate; sodium tetrahydroborate / dichloromethane; methanol / 0.5 h / -20 °C
2.1: dihydrogen peroxide; molybdenum(VI) oxide / acetonitrile / 24 h
3.1: pyridine; acetic anhydride / dichloromethane / 2 h / 20 °C
4.1: toluene / 72 h / Reflux
5.1: potassium iodide; chloro-trimethyl-silane / acetonitrile / 0.58 h / 20 °C
6.1: chloro-trimethyl-silane; 1H-imidazole / dichloromethane / 0.5 h / 20 °C
6.2: 0.25 h / 20 °C
7.1: lithium hydroxide / tetrahydrofuran; water / 18 h
8.1: triphenylphosphine; di-isopropyl azodicarboxylate / 3 h / 0 °C
9.1: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
Multi-step reaction with 9 steps
1.1: cerium(III) chloride heptahydrate; sodium tetrahydroborate / dichloromethane; methanol / 0.5 h / -20 °C
2.1: dihydrogen peroxide; molybdenum(VI) oxide / acetonitrile / 24 h
3.1: pyridine; acetic anhydride / dichloromethane / 2 h / 20 °C
4.1: scandium tris(trifluoromethanesulfonate) / toluene / 72 h / 30 °C / Molecular sieve
5.1: potassium iodide; chloro-trimethyl-silane / acetonitrile / 0.58 h / 20 °C
6.1: chloro-trimethyl-silane; 1H-imidazole / dichloromethane / 0.5 h / 20 °C
6.2: 0.25 h / 20 °C
7.1: lithium hydroxide / tetrahydrofuran; water / 18 h
8.1: triphenylphosphine; di-isopropyl azodicarboxylate / 3 h / 0 °C
9.1: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
(3S,4S,6S)-3-((S)-(4-(benzyloxy)phenyl)(4-fluorophenylamino)methyl)-6-(4-fluorophenyl)-4-hydroxytetrahydro-2H-pyran-2-one

(3S,4S,6S)-3-((S)-(4-(benzyloxy)phenyl)(4-fluorophenylamino)methyl)-6-(4-fluorophenyl)-4-hydroxytetrahydro-2H-pyran-2-one

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 3 steps
1: Burgess Reagent / toluene / 18 h / 90 °C
2: platinum(IV) oxide; hydrogen / toluene / 20 °C / 750.08 Torr
3: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
(6S)-3-((R)-(4-(benzyloxy)phenyl)(4-fluorophenylamino)-methyl)-6-(4-fluorophenyl)-5,6-dihydro-2H-pyran-2-one
1416263-38-1

(6S)-3-((R)-(4-(benzyloxy)phenyl)(4-fluorophenylamino)-methyl)-6-(4-fluorophenyl)-5,6-dihydro-2H-pyran-2-one

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: platinum(IV) oxide; hydrogen / toluene / 20 °C / 750.08 Torr
2: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
4-fluorobenzaldehyde
459-57-4

4-fluorobenzaldehyde

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 10 steps
1.1: [(R,R)-salen-Cr]BF4 / tert-butyl methyl ether / 24 h / -30 °C / Molecular sieve
1.2: 5 h / 20 °C
2.1: cerium(III) chloride heptahydrate; sodium tetrahydroborate / dichloromethane; methanol / 0.5 h / -20 °C
3.1: dihydrogen peroxide; molybdenum(VI) oxide / acetonitrile / 24 h
4.1: pyridine; acetic anhydride / dichloromethane / 2 h / 20 °C
5.1: toluene / 72 h / Reflux
6.1: potassium iodide; chloro-trimethyl-silane / acetonitrile / 0.58 h / 20 °C
7.1: chloro-trimethyl-silane; 1H-imidazole / dichloromethane / 0.5 h / 20 °C
7.2: 0.25 h / 20 °C
8.1: lithium hydroxide / tetrahydrofuran; water / 18 h
9.1: triphenylphosphine; di-isopropyl azodicarboxylate / 3 h / 0 °C
10.1: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
Multi-step reaction with 10 steps
1.1: [(R,R)-salen-Cr]BF4 / tert-butyl methyl ether / 24 h / -30 °C / Molecular sieve
1.2: 5 h / 20 °C
2.1: cerium(III) chloride heptahydrate; sodium tetrahydroborate / dichloromethane; methanol / 0.5 h / -20 °C
3.1: dihydrogen peroxide; molybdenum(VI) oxide / acetonitrile / 24 h
4.1: pyridine; acetic anhydride / dichloromethane / 2 h / 20 °C
5.1: scandium tris(trifluoromethanesulfonate) / toluene / 72 h / 30 °C / Molecular sieve
6.1: potassium iodide; chloro-trimethyl-silane / acetonitrile / 0.58 h / 20 °C
7.1: chloro-trimethyl-silane; 1H-imidazole / dichloromethane / 0.5 h / 20 °C
7.2: 0.25 h / 20 °C
8.1: lithium hydroxide / tetrahydrofuran; water / 18 h
9.1: triphenylphosphine; di-isopropyl azodicarboxylate / 3 h / 0 °C
10.1: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
Multi-step reaction with 11 steps
1.1: [(R,R)-salen-Cr]BF4 / tert-butyl methyl ether / 24 h / -30 °C / Molecular sieve
1.2: 5 h / 20 °C
2.1: cerium(III) chloride heptahydrate; sodium tetrahydroborate / dichloromethane; methanol / 0.5 h / -20 °C
3.1: dihydrogen peroxide; molybdenum(VI) oxide / acetonitrile / 24 h
4.1: pyridine; acetic anhydride / dichloromethane / 2 h / 20 °C
5.1: toluene / 72 h / Reflux
6.1: lithium hydroxide monohydrate / tetrahydrofuran; water / 18 h
7.1: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran / 3 h / 0 °C
8.1: potassium iodide / acetonitrile; water / 0.58 h / 20 °C
9.1: Burgess Reagent / toluene / 18 h / 90 °C
10.1: platinum(IV) oxide; hydrogen / toluene / 20 °C / 750.08 Torr
11.1: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
Multi-step reaction with 11 steps
1.1: [(R,R)-salen-Cr]BF4 / tert-butyl methyl ether / 24 h / -30 °C / Molecular sieve
1.2: 5 h / 20 °C
2.1: cerium(III) chloride heptahydrate; sodium tetrahydroborate / dichloromethane; methanol / 0.5 h / -20 °C
3.1: dihydrogen peroxide; molybdenum(VI) oxide / acetonitrile / 24 h
4.1: pyridine; acetic anhydride / dichloromethane / 2 h / 20 °C
5.1: scandium tris(trifluoromethanesulfonate) / toluene / 72 h / 30 °C / Molecular sieve
6.1: lithium hydroxide monohydrate / tetrahydrofuran; water / 18 h
7.1: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran / 3 h / 0 °C
8.1: potassium iodide / acetonitrile; water / 0.58 h / 20 °C
9.1: Burgess Reagent / toluene / 18 h / 90 °C
10.1: platinum(IV) oxide; hydrogen / toluene / 20 °C / 750.08 Torr
11.1: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
(2R)-2-(4-fluorophenyl)-3,4-dihydro-2H-pyran-4-ol
1416263-27-8

(2R)-2-(4-fluorophenyl)-3,4-dihydro-2H-pyran-4-ol

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 8 steps
1.1: dihydrogen peroxide; molybdenum(VI) oxide / acetonitrile / 24 h
2.1: pyridine; acetic anhydride / dichloromethane / 2 h / 20 °C
3.1: toluene / 72 h / Reflux
4.1: potassium iodide; chloro-trimethyl-silane / acetonitrile / 0.58 h / 20 °C
5.1: chloro-trimethyl-silane; 1H-imidazole / dichloromethane / 0.5 h / 20 °C
5.2: 0.25 h / 20 °C
6.1: lithium hydroxide / tetrahydrofuran; water / 18 h
7.1: triphenylphosphine; di-isopropyl azodicarboxylate / 3 h / 0 °C
8.1: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
Multi-step reaction with 8 steps
1.1: dihydrogen peroxide; molybdenum(VI) oxide / acetonitrile / 24 h
2.1: pyridine; acetic anhydride / dichloromethane / 2 h / 20 °C
3.1: scandium tris(trifluoromethanesulfonate) / toluene / 72 h / 30 °C / Molecular sieve
4.1: potassium iodide; chloro-trimethyl-silane / acetonitrile / 0.58 h / 20 °C
5.1: chloro-trimethyl-silane; 1H-imidazole / dichloromethane / 0.5 h / 20 °C
5.2: 0.25 h / 20 °C
6.1: lithium hydroxide / tetrahydrofuran; water / 18 h
7.1: triphenylphosphine; di-isopropyl azodicarboxylate / 3 h / 0 °C
8.1: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
Multi-step reaction with 9 steps
1: dihydrogen peroxide; molybdenum(VI) oxide / acetonitrile / 24 h
2: pyridine; acetic anhydride / dichloromethane / 2 h / 20 °C
3: toluene / 72 h / Reflux
4: lithium hydroxide monohydrate / tetrahydrofuran; water / 18 h
5: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran / 3 h / 0 °C
6: potassium iodide / acetonitrile; water / 0.58 h / 20 °C
7: Burgess Reagent / toluene / 18 h / 90 °C
8: platinum(IV) oxide; hydrogen / toluene / 20 °C / 750.08 Torr
9: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
Multi-step reaction with 9 steps
1: dihydrogen peroxide; molybdenum(VI) oxide / acetonitrile / 24 h
2: pyridine; acetic anhydride / dichloromethane / 2 h / 20 °C
3: scandium tris(trifluoromethanesulfonate) / toluene / 72 h / 30 °C / Molecular sieve
4: lithium hydroxide monohydrate / tetrahydrofuran; water / 18 h
5: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran / 3 h / 0 °C
6: potassium iodide / acetonitrile; water / 0.58 h / 20 °C
7: Burgess Reagent / toluene / 18 h / 90 °C
8: platinum(IV) oxide; hydrogen / toluene / 20 °C / 750.08 Torr
9: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
4-hydroxy-benzaldehyde
123-08-0

4-hydroxy-benzaldehyde

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 8 steps
1.1: potassium carbonate; potassium iodide / tetrahydrofuran / 20 h / Reflux
2.1: methanesulfonic acid / acetone / 2 h / 20 °C
3.1: toluene / 72 h / Reflux
4.1: potassium iodide; chloro-trimethyl-silane / acetonitrile / 0.58 h / 20 °C
5.1: chloro-trimethyl-silane; 1H-imidazole / dichloromethane / 0.5 h / 20 °C
5.2: 0.25 h / 20 °C
6.1: lithium hydroxide / tetrahydrofuran; water / 18 h
7.1: triphenylphosphine; di-isopropyl azodicarboxylate / 3 h / 0 °C
8.1: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
Multi-step reaction with 8 steps
1.1: potassium carbonate; potassium iodide / tetrahydrofuran / 20 h / Reflux
2.1: methanesulfonic acid / acetone / 2 h / 20 °C
3.1: scandium tris(trifluoromethanesulfonate) / toluene / 72 h / 30 °C / Molecular sieve
4.1: potassium iodide; chloro-trimethyl-silane / acetonitrile / 0.58 h / 20 °C
5.1: chloro-trimethyl-silane; 1H-imidazole / dichloromethane / 0.5 h / 20 °C
5.2: 0.25 h / 20 °C
6.1: lithium hydroxide / tetrahydrofuran; water / 18 h
7.1: triphenylphosphine; di-isopropyl azodicarboxylate / 3 h / 0 °C
8.1: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
Multi-step reaction with 9 steps
1: potassium carbonate; potassium iodide / tetrahydrofuran / 20 h / Reflux
2: methanesulfonic acid / acetone / 2 h / 20 °C
3: toluene / 72 h / Reflux
4: lithium hydroxide monohydrate / tetrahydrofuran; water / 18 h
5: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran / 3 h / 0 °C
6: potassium iodide / acetonitrile; water / 0.58 h / 20 °C
7: Burgess Reagent / toluene / 18 h / 90 °C
8: platinum(IV) oxide; hydrogen / toluene / 20 °C / 750.08 Torr
9: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
Multi-step reaction with 9 steps
1: potassium carbonate; potassium iodide / tetrahydrofuran / 20 h / Reflux
2: methanesulfonic acid / acetone / 2 h / 20 °C
3: scandium tris(trifluoromethanesulfonate) / toluene / 72 h / 30 °C / Molecular sieve
4: lithium hydroxide monohydrate / tetrahydrofuran; water / 18 h
5: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran / 3 h / 0 °C
6: potassium iodide / acetonitrile; water / 0.58 h / 20 °C
7: Burgess Reagent / toluene / 18 h / 90 °C
8: platinum(IV) oxide; hydrogen / toluene / 20 °C / 750.08 Torr
9: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
Multi-step reaction with 5 steps
1.1: potassium carbonate / 12 h / 20 °C
1.2: 4 h / Reflux
2.1: N-ethyl-N,N-diisopropylamine; titanium(IV) isopropylate; titanium tetrachloride / dichloromethane / 3 h / -5 °C
3.1: N,O-Bis(trimethylsilyl)acetamide; tetrabutyl ammonium fluoride / toluene / 48 h / Reflux
4.1: formic acid / dichloromethane / 12 h / Reflux
5.1: dimethyl sulfide borane / dichloromethane; toluene; tetrahydrofuran / 12 h / 15 °C
View Scheme
benzyl chloride
100-44-7

benzyl chloride

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 8 steps
1.1: potassium carbonate; potassium iodide / tetrahydrofuran / 20 h / Reflux
2.1: methanesulfonic acid / acetone / 2 h / 20 °C
3.1: toluene / 72 h / Reflux
4.1: potassium iodide; chloro-trimethyl-silane / acetonitrile / 0.58 h / 20 °C
5.1: chloro-trimethyl-silane; 1H-imidazole / dichloromethane / 0.5 h / 20 °C
5.2: 0.25 h / 20 °C
6.1: lithium hydroxide / tetrahydrofuran; water / 18 h
7.1: triphenylphosphine; di-isopropyl azodicarboxylate / 3 h / 0 °C
8.1: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
Multi-step reaction with 8 steps
1.1: potassium carbonate; potassium iodide / tetrahydrofuran / 20 h / Reflux
2.1: methanesulfonic acid / acetone / 2 h / 20 °C
3.1: scandium tris(trifluoromethanesulfonate) / toluene / 72 h / 30 °C / Molecular sieve
4.1: potassium iodide; chloro-trimethyl-silane / acetonitrile / 0.58 h / 20 °C
5.1: chloro-trimethyl-silane; 1H-imidazole / dichloromethane / 0.5 h / 20 °C
5.2: 0.25 h / 20 °C
6.1: lithium hydroxide / tetrahydrofuran; water / 18 h
7.1: triphenylphosphine; di-isopropyl azodicarboxylate / 3 h / 0 °C
8.1: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
Multi-step reaction with 9 steps
1: potassium carbonate; potassium iodide / tetrahydrofuran / 20 h / Reflux
2: methanesulfonic acid / acetone / 2 h / 20 °C
3: toluene / 72 h / Reflux
4: lithium hydroxide monohydrate / tetrahydrofuran; water / 18 h
5: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran / 3 h / 0 °C
6: potassium iodide / acetonitrile; water / 0.58 h / 20 °C
7: Burgess Reagent / toluene / 18 h / 90 °C
8: platinum(IV) oxide; hydrogen / toluene / 20 °C / 750.08 Torr
9: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
Multi-step reaction with 9 steps
1: potassium carbonate; potassium iodide / tetrahydrofuran / 20 h / Reflux
2: methanesulfonic acid / acetone / 2 h / 20 °C
3: scandium tris(trifluoromethanesulfonate) / toluene / 72 h / 30 °C / Molecular sieve
4: lithium hydroxide monohydrate / tetrahydrofuran; water / 18 h
5: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran / 3 h / 0 °C
6: potassium iodide / acetonitrile; water / 0.58 h / 20 °C
7: Burgess Reagent / toluene / 18 h / 90 °C
8: platinum(IV) oxide; hydrogen / toluene / 20 °C / 750.08 Torr
9: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
p-benzyloxybenzaldehyde
4397-53-9

p-benzyloxybenzaldehyde

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 7 steps
1.1: methanesulfonic acid / acetone / 2 h / 20 °C
2.1: toluene / 72 h / Reflux
3.1: potassium iodide; chloro-trimethyl-silane / acetonitrile / 0.58 h / 20 °C
4.1: chloro-trimethyl-silane; 1H-imidazole / dichloromethane / 0.5 h / 20 °C
4.2: 0.25 h / 20 °C
5.1: lithium hydroxide / tetrahydrofuran; water / 18 h
6.1: triphenylphosphine; di-isopropyl azodicarboxylate / 3 h / 0 °C
7.1: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
Multi-step reaction with 7 steps
1.1: methanesulfonic acid / acetone / 2 h / 20 °C
2.1: scandium tris(trifluoromethanesulfonate) / toluene / 72 h / 30 °C / Molecular sieve
3.1: potassium iodide; chloro-trimethyl-silane / acetonitrile / 0.58 h / 20 °C
4.1: chloro-trimethyl-silane; 1H-imidazole / dichloromethane / 0.5 h / 20 °C
4.2: 0.25 h / 20 °C
5.1: lithium hydroxide / tetrahydrofuran; water / 18 h
6.1: triphenylphosphine; di-isopropyl azodicarboxylate / 3 h / 0 °C
7.1: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
Multi-step reaction with 8 steps
1: methanesulfonic acid / acetone / 2 h / 20 °C
2: toluene / 72 h / Reflux
3: lithium hydroxide monohydrate / tetrahydrofuran; water / 18 h
4: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran / 3 h / 0 °C
5: potassium iodide / acetonitrile; water / 0.58 h / 20 °C
6: Burgess Reagent / toluene / 18 h / 90 °C
7: platinum(IV) oxide; hydrogen / toluene / 20 °C / 750.08 Torr
8: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

ezetemibe
163222-33-1

ezetemibe

Conditions
ConditionsYield
With 10 wt% Pd(OH)2 on carbon; hydrogen In methanol; cyclohexane at 70℃; under 760.051 Torr; for 3h;99%
With 5%-palladium/activated carbon; hydrogen In tetrahydrofuran; ethanol at 50 - 55℃; under 37.5038 - 75.0075 Torr;90.3%
With palladium 10% on activated carbon; ammonium formate; acetic acid for 6h; Reflux;90%
L-N-Boc-Ala
15761-38-3

L-N-Boc-Ala

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

(1S)-3-[(2S,3R)-2-[4-(benzyloxy)phenyl]-1-(4-fluorophenyl)-4-oxoazetidin-3-yl]-1-(4-fluorophenyl)propyl (2S)-2-{[(tert-butoxy)carbonyl]amino}propanoate

(1S)-3-[(2S,3R)-2-[4-(benzyloxy)phenyl]-1-(4-fluorophenyl)-4-oxoazetidin-3-yl]-1-(4-fluorophenyl)propyl (2S)-2-{[(tert-butoxy)carbonyl]amino}propanoate

Conditions
ConditionsYield
With dmap; dicyclohexyl-carbodiimide In dichloromethane Inert atmosphere;69%
(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

1-(4-fluorophenyl)-(3R)-[(4-fluorophenyl)-(2E)-propenyl]-(4S)-(4-hydroxyphenyl)-2-azetidinone

1-(4-fluorophenyl)-(3R)-[(4-fluorophenyl)-(2E)-propenyl]-(4S)-(4-hydroxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: H2 / 10percent Pd/C / ethanol / 16 h / 3102.9 Torr
2: p-TsOH*H2O / toluene / 6 h / 80 °C
View Scheme
(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

4(S)-(4-acetyloxyphenyl)-3(R)-(3(S)-acetyloxy-3-(4-fluorophenyl)propyl)-1-(4-fluorophenyl)-2-azetidinone
163380-20-9

4(S)-(4-acetyloxyphenyl)-3(R)-(3(S)-acetyloxy-3-(4-fluorophenyl)propyl)-1-(4-fluorophenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: H2 / 10percent Pd/C / ethanol / 16 h / 3102.9 Torr
2: 0.260 g / pyridine / CH2Cl2 / 1 h / 22 °C
View Scheme
(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

A

EZT-FAM
1197811-72-5

EZT-FAM

B

ezetemibe
163222-33-1

ezetemibe

Conditions
ConditionsYield
With formic acid; ammonium formate; 5%-palladium/activated carbon In methanol at 20℃; Product distribution / selectivity; Inert atmosphere;

163222-32-0Relevant articles and documents

Chiral amino-pyridine-phosphine tridentate ligand, manganese complex, and preparation method and application thereof

-

Paragraph 0597-0600; 0603, (2020/07/13)

The invention discloses a chiral amino-pyridine-phosphine tridentate ligand, a manganese complex, and a preparation method and application thereof. The chiral amino-pyridine-phosphine tridentate ligand is shown as a formula II, and the manganese complex of the chiral amino-pyridine-phosphine tridentate ligand can be used for efficiently catalyzing and hydrogenating ketone compounds to prepare chiral alcohol compounds in a high enantioselectivity mode. The chiral amino-pyridine-phosphine tridentate ligand and the manganese complex are simple in synthesis process, good in stability, high in catalytic activity and mild in reaction conditions.

METHOD OF PREPARING EZETIMIBE AND INTERMEDIATE THEREOF

-

, (2019/08/30)

Disclosed is a method of preparing ezetimibe, including cross-metathesis using a Grubbs 2nd catalyst and deprotection using a Pearlman's catalyst, and an intermediate thereof. The method of preparing ezetimibe is useful as an efficient ezetimibe synthesis technique in pharmaceutical fields using ezetimibe as a raw material.

Lutidine-Based Chiral Pincer Manganese Catalysts for Enantioselective Hydrogenation of Ketones

Zhang, Linli,Tang, Yitian,Han, Zhaobin,Ding, Kuiling

supporting information, p. 4973 - 4977 (2019/03/17)

A series of MnI complexes containing lutidine-based chiral pincer ligands with modular and tunable structures has been developed. The complex shows unprecedentedly high activities (up to 9800 TON; TON=turnover number), broad substrate scope (81 examples), good functional-group tolerance, and excellent enantioselectivities (85–98 % ee) in the hydrogenation of various ketones. These aspects are rare in earth-abundant metal catalyzed hydrogenations. The utility of the protocol have been demonstrated in the asymmetric synthesis of a variety of key intermediates for chiral drugs. Preliminary mechanistic investigations indicate that an outer-sphere mode of substrate–catalyst interactions probably dominates the catalysis.

Preparation method of ezetimibe for treating hyperlipidemia

-

, (2018/03/25)

The invention discloses a preparation method of ezetimibe for treating hyperlipidemia, and belongs to the field of drug synthesizing. The method is characterized in that a compound 2 is treated as theraw material and subjected to four synthesizing steps to prepare ezetimibe 1, wherein the four steps include the step of protection for carbonyl group, cyclizing, carbonyl reduction and hydrogenationdeprotection. Compared with methods in existing documents, the preparation method has the advantages that the use of polluting titanium agents is avoided; the synthesizing steps are decreased; the technology stability is improved; massive production can be performed.

Chiral Cyclohexyl-Fused Spirobiindanes: Practical Synthesis, Ligand Development, and Asymmetric Catalysis

Zheng, Zhiyao,Cao, Yuxi,Chong, Qinglei,Han, Zhaobin,Ding, Jiaming,Luo, Chenguang,Wang, Zheng,Zhu, Dongsheng,Zhou, Qi-Lin,Ding, Kuiling

supporting information, p. 10374 - 10381 (2018/08/03)

1,1′-Spirobiindane has been one type of privileged skeleton for chiral ligand design, and 1,1′-spirobiindane-based chiral ligands have demonstrated outstanding performance in various asymmetric catalysis. However, the access to enantiopure spirobiindane is quite tedious, which obstructs its practical application. In the present article, a facile enantioselective synthesis of cyclohexyl-fused chiral spirobiindanes has been accomplished, in high yields and excellent stereoselectivities (up to >99% ee), via a sequence of Ir-catalyzed asymmetric hydrogenation of α,α′-bis(arylidene)ketones and TiCl4 promoted asymmetric spiroannulation of the hydrogenated chiral ketones. The protocol can be performed in one pot and is readily scalable, and has been utilized in a 25 g scale asymmetric synthesis of cyclohexyl-fused spirobiindanediol (1S,2S,2′S)-5, in >99% ee and 67% overall yield for four steps without chromatographic purification. Facile derivations of (1S,2S,2′S)-5 provided straightforward access to chiral monodentate phosphoramidites 6a-c and a tridentate phosphorus-amidopyridine 11, which were evaluated as chiral ligands in several benchmark enantioselective reactions (hydrogenation, hydroacylation, and [2 + 2] reaction) catalyzed by transition metal (Rh, Au, or Ir). Preliminary results from comparative studies showcased the excellent catalytic performances of these ligands, with a competency essentially equal to the corresponding well-established privileged ligands bearing a regular spirobiindane backbone. X-ray crystallography revealed a close resemblance between the structures of the precatalysts 20 and 21 and their analogues, which ultimately help to rationalize the almost identical stereochemical outcomes of reactions catalyzed by metal complexes of spirobiindane-derived ligands with or without a fused cyclohexyl ring on the backbone. This work is expected to stimulate further applications of this type of readily accessible skeletons in development of chiral ligands and functional molecules.

Ezetimibe intermediate, synthesis method of intermediate and synthesis method of ezetimibe

-

, (2017/07/01)

The invention provides an ezetimibe intermediate, a synthesis method of the intermediate and a synthesis method of ezetimibe. The method is short in synthetic route. The method includes the steps of making fluorobenzene as the initial raw material sequentially have acylation reaction with glutaric anhydride and 4(S)-4-phenyl oxazolidinone to generate a compound II, protecting carbonyl through 2,2-bis-substituted-1,3-propylene glycol to obtain a compound III, generating a compound V through the compound III and a compound IV under the catalysis of titanium tetrachloride, cyclizing the compound V to generate a compound VI, hydrolyzing the compound VI to obtain a compound VII, and reducing the compound VII through a borane chiral reducing agent and removing a benzyl protecting group in a hydrogenated mode to obtain the ezetimibe. The method is high in yield, little in side reaction and suitable for industrial mass production.

Substituted phosphoramidate derivative, method for preparing thereof, and use thereof definitions of substituent groups in general formula (I) are the same as those defined in the specification

-

Page/Page column 18; 19; 20, (2018/03/23)

The present invention relates to a substituted phosphoramidate derivative represented by general formula (I), a method for preparing therefor, and use thereof. In the general formula (I), A is selected from a phenyl group or a naphthyl group, and the phenyl group or the naphthyl group is optionally further substituted with 0 to 5 substituents selected from H, F, Cl, Br, I, an amino group, a hydroxy group, a carboxy group, a C1-4 alkyl group or a C1-4 alkoxy group. B is ; E is selected from -CH(CH2F)CH2-, CH2CH(CH3)OCH2- or -CH2-CH2OCH2-; R1 is selected from H or a C1-4 alkyl group; R2 is a natural or pharmaceutically acceptable amino acid side chain, if the side chain contains a carboxyl group, the carboxyl group may be optionally esterified with an alkyl group or an aryl group; R3 is ; R4 is a group selected from H, a methylacyl group, a C1-4 alkyl group, a -(CH2)n-C3-6 carbocyclic ring, a -(C= O)-C1-4 alkyl group or a -(C = O)-C1-4 carbocyclic ring; n is selected from 0, 1 or 2.

MANUFACTURING METHOD OF (3R,4S)-1-(4-FLUOROPHENYL)-[3(S)-HYDROXY-3-(4-FLUOROPHENYL)PROPYL]-[4-(PHENYLMETHOXY)PHENYL]-2-AZETIDINONE

-

, (2017/11/18)

PROBLEM TO BE SOLVED: To provide a method for effectively manufacturing high purity (3R,4S)-1-(4-fluorophenyl)-[3(S)-hydroxy-3-(4-fluorophenyl)propyl]-[4-(phenylmethoxy)phenyl]-2-azetidinone with reduced contents of specific impurities and enantiomers. SOLUTION: When a benzyl protective body is manufactured by reacting a benzyl protective keto body and borane in presence of a CBS catalyst, the benzyl protective keto body is injected under a condition with co-existing a part of borane of needed amount in a reaction system in advance and remaining borane is added later to conduct the reaction. SELECTED DRAWING: None COPYRIGHT: (C)2017,JPOandINPIT

Ezetimibe preparation method

-

Paragraph 0053; 0054; 0055; 0058; 0060; 0062; 0064; 0067, (2017/08/29)

The invention solves the problem of providing a zetimibe preparation method. The ezetimibe preparation method is high in yield rate, few in impurities, simple in operation and operable and controllable during scale-up. The ezetimibe preparation method improves the preparation method of a key intermediate of EZ2 ((3R, S4)-1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-benzyloxy-phenyl)-2-azetidinone). The ezetimibe preparation method reduces the reaction temperature, simplifies operation, improves the product yield rate and reduces the content of isomer impurities. Compared with existing preparation methods, the ezetimibe preparation method can avoid low-temperature reaction, improve the production efficiency and the product yield rate and facilitate scale production of ezetimibe. The synthetic route applied in the ezetimibe preparation method is shown as below.

Preparation process of ezetimibe and its intermediate

-

Paragraph 0053-0055, (2017/09/13)

The invention provides a preparation process of ezetimibe shown as formula II and its intermediate. The process includes the steps of: in an organic solvent, and under the catalysis of (R)-Me-CBS, subjecting compound I to asymmetric reduction reaction shown as the specification in an NaBH4-I2 reduction system so as to obtain II. Specifically, R is hydrogen atom, benzyl, t-butyldimethylsilyl or trimethylsilyl. In the preparation method, the used NaBH4-I2 reduction system is more environment-friendly than borane dimethylsulfide, the operation is safer and more convenient, also the product cost can be reduced, and the obtained product has high yield and chiral purity. Therefore the preparation process can be used for synthesis of ezetimibe smoothly, and is more suitable for industrial production.

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