189028-95-3

Basic information

• Product Name: (4S)-3-[(5R)-5-(4-FLUOROPHENYL)-5-HYDROXYPENTANOYL]-4-PHENYL-1,3-OXAZOLIDIN-2-ONE
• Synonyms: (4S)-3-[(5R)-5-(4-FLUOROPHENYL)-5-HYDROXYPENTANOYL]-4-PHENYL-1,3-OXAZOLIDIN-2-ONE;(4S)-3-[(5S)-5-(4-Fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidin-2-one;(4S)-4-Phenyl-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-1,3-oxazolidin-2-one;(4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxy-1-oxo-pentyl]-4-phenyl-2-Oxazolidinone;EzetiMibe InterMediates;3-[(5S)-5-(4-fluorophenyl)-5-hydroxy-1-oxopentyl]-4-phenyl-, (4S)- 2-Oxazolidinone;2-Oxazolidinone, 3-[(5S)-5-(4-fluorophenyl)-5-hydroxy-1-oxopentyl]-4-phenyl-, (4S)-;Ezetimibe INT A
• CAS NO: 189028-95-3
• Molecular Formula: C₂₀H₂₀FNO₄
• Molecular Weight: 357.38
• EINECS: 1308068-626-2
• Product Categories: Ezetimibe intermediates;Ezetimibe
• Mol File: 189028-95-3.mol

Chemical Properties

• Boiling Point: 572.727 °C at 760 mmHg
• Flash Point: 300.174 °C
• Appearance: /
• Density: 1.297
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.588
• Storage Temp.: 2-8°C
• PKA: 14.17±0.20(Predicted)
• CAS DataBase Reference: (4S)-3-[(5R)-5-(4-FLUOROPHENYL)-5-HYDROXYPENTANOYL]-4-PHENYL-1,3-OXAZOLIDIN-2-ONE(CAS DataBase Reference)
• NIST Chemistry Reference: (4S)-3-[(5R)-5-(4-FLUOROPHENYL)-5-HYDROXYPENTANOYL]-4-PHENYL-1,3-OXAZOLIDIN-2-ONE(189028-95-3)
• EPA Substance Registry System: (4S)-3-[(5R)-5-(4-FLUOROPHENYL)-5-HYDROXYPENTANOYL]-4-PHENYL-1,3-OXAZOLIDIN-2-ONE(189028-95-3)

Safety Data

• Hazardous Substances Data: 189028-95-3(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(4S)-3-[(5R)-5-(4-FLUOROPHENYL)-5-HYDROXYPENTANOYL]-4-PHENYL-1,3-OXAZOLIDIN-2-ONE is used as a pharmaceutical intermediate for the preparation of ezetimibe, an antihyperlipoproteinemic drug. Ezetimibe functions as a cholesterol absorption inhibitor, helping to lower patients' plasma cholesterol levels and thereby reducing the risk of cardiovascular diseases.
Additionally, due to its antimicrobial properties, this compound may also find applications in the development of new antibiotics or antifungal agents, contributing to the fight against drug-resistant infections. However, further research and development would be necessary to explore these potential uses.

References

http://www.cphi-online.com/ezetimibe-intermediate-4s3-prod587443.html https://en.wikipedia.org/wiki/2-Oxazolidone

InChI:InChI=1/C20H20FNO4/c21-16-11-9-15(10-12-16)18(23)7-4-8-19(24)22-17(13-26-20(22)25)14-5-2-1-3-6-14/h1-3,5-6,9-12,17-18,23H,4,7-8,13H2/t17-,18+/m1/s1

Synthetic route

(S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione (189028-93-1) → (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3)

Conditions	Yield
Stage #1: (S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione With TarB-N02 In tetrahydrofuran at 20℃; for 0.5h; Stage #2: With lithium borohydride In tetrahydrofuran for 0.666667h; Reagent/catalyst; enantioselective reaction;	96%
Stage #1: (S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione With dimethylsulfide borane complex; (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole In dichloromethane; toluene at -5 - 0℃; for 4 - 6h; Stage #2: With sulfuric acid; dihydrogen peroxide In methanol; dichloromethane; water; toluene for 0.25h;	95%
Stage #1: With dimethylsulfide borane complex; (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole In dichloromethane; toluene at -5 - 0℃; for 0.25h; Stage #2: (S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione In dichloromethane; toluene at -5 - 0℃; for 4 - 6h;	95%

vinyl acetate (108-05-4) + (R,S)-3-[5-(4-fluorophenyl)-5-hydroxy-pentanoyl]-4-phenyl-oxazolidin-2-one (1246853-48-4) → (R)-1-(4-fluorophenyl)-5-oxo-5-[(S)-2-oxo-4-phenyloxazolidin-3-yl]pentyl acetate (1246853-49-5) + (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3)

Conditions	Yield
Lipozyme TL IM In toluene at 20 - 40℃; Product distribution / selectivity;	A 68% B 74%
With Candida rugosa lipase In di-isopropyl ether at 35℃; for 120h; Solvent; Reagent/catalyst; Concentration; Enzymatic reaction;	A n/a B n/a

(S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione (189028-93-1) → (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3) + (4S)-3-[(5R)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidin-2-one + (S)-3-[(S)-5-(4-Fluoro-phenyl)-1,5-dihydroxy-pentyl]-4-phenyl-oxazolidin-2-one

Conditions	Yield
With borane-THF; boron trifluoride diethyl etherate; (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole In tetrahydrofuran at 25℃; Product distribution; Further Variations:; Catalysts; Temperatures; acid additives, water content;
With BH3-DEA; (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole In tetrahydrofuran; 1,2-dimethoxyethane; toluene at 40℃;

(S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione (189028-93-1) → (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3) + (S)-3-[(S)-5-(4-Fluoro-phenyl)-1,5-dihydroxy-pentyl]-4-phenyl-oxazolidin-2-one

Conditions	Yield
With sodium tetrahydroborate; dimethyl sulfate; N,N-diethylaniline; (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole In tetrahydrofuran; toluene at 20℃; Product distribution; Further Variations:; Reagents; Temperatures;	A 13 g B n/a

(S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione (189028-93-1) → (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3) + (4S)-3-[(5R)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidin-2-one

Conditions	Yield
Stage #1: (S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione With borane N,N-diethylaniline complex; (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole In tetrahydrofuran; toluene at 18 - 20℃; for 1h; Stage #2: With water; potassium carbonate In tetrahydrofuran; toluene at 20 - 30℃; for 0.5h;
Stage #1: (S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione With sodium tetrahydroborate; chloro-trimethyl-silane; (R)-α,α-diphenylprolinol In tetrahydrofuran at 24℃; for 3h; Heating / reflux; Stage #2: With hydrogenchloride; water In tetrahydrofuran; toluene at 4℃; for 0.5h; Product distribution / selectivity;	A n/a B n/a
Stage #1: (S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione With sodium tetrahydroborate; chloro-trimethyl-silane; (R)-2-[bis(4-trifluorophenyl)hydroxymethyl]pyrrolidine In tetrahydrofuran at 24℃; for 3h; Heating / reflux; Stage #2: With hydrogenchloride; water In tetrahydrofuran; toluene at 4℃; for 0.5h; Product distribution / selectivity;	A n/a B n/a
With chloro[(1S,2S)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine]-(mesitylene) ruthenium (II); formic acid/triethylamine complex 5:2 In tert-butyl methyl ether at 42℃; Reagent/catalyst; Solvent; Temperature; Inert atmosphere; stereoselective reaction;	A n/a B n/a

isopropyl alcohol (67-63-0) + (S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione (189028-93-1) → (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3)

Conditions	Yield
With magnesium sulfate In triethanolamine(chloride)

C24H26FNO5 → (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: Candida rugosa lipase / di-isopropyl ether; aq. phosphate buffer / 120 h / 40 °C / Enzymatic reaction 2: Candida antarctica B lipase / toluene / 120 h / 35 °C / Enzymatic reaction View Scheme
Multi-step reaction with 2 steps 1: Candida rugosa lipase / di-isopropyl ether; aq. phosphate buffer / 120 h / 40 °C / Enzymatic reaction 2: Candida antarctica B lipase / toluene / 120 h / 35 °C / Enzymatic reaction View Scheme

C24H26FNO5 → (R)-1-(4-fluorophenyl)-5-oxo-5-[(S)-2-oxo-4-phenyloxazolidin-3-yl]pentyl acetate (1246853-49-5) + (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: Candida rugosa lipase / di-isopropyl ether; aq. phosphate buffer / 120 h / 40 °C / Enzymatic reaction 2: Candida rugosa lipase / di-isopropyl ether / 120 h / 35 °C / Enzymatic reaction View Scheme
Multi-step reaction with 3 steps 1: Candida rugosa lipase / di-isopropyl ether; aq. phosphate buffer / 120 h / 40 °C / Enzymatic reaction 2: triethylamine; dmap / dichloromethane / 4 h / 0 °C 3: Candida rugosa lipase / di-isopropyl ether; aq. phosphate buffer / 120 h / 40 °C / pH 6.2 / Enzymatic reaction View Scheme

C24H26FNO5 → (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: Candida rugosa lipase / di-isopropyl ether; aq. phosphate buffer / 120 h / 40 °C / Enzymatic reaction 2: Candida antarctica B lipase / toluene / 120 h / 35 °C / Enzymatic reaction View Scheme
Multi-step reaction with 2 steps 1: Candida rugosa lipase / di-isopropyl ether; aq. phosphate buffer / 120 h / 40 °C / Enzymatic reaction 2: Candida antarctica B lipase / toluene / 120 h / 35 °C / Enzymatic reaction View Scheme

C24H26FNO5 → (R)-1-(4-fluorophenyl)-5-oxo-5-[(S)-2-oxo-4-phenyloxazolidin-3-yl]pentyl acetate (1246853-49-5) + (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: Candida rugosa lipase / di-isopropyl ether; aq. phosphate buffer / 120 h / 40 °C / Enzymatic reaction 2: Candida rugosa lipase / di-isopropyl ether / 120 h / 35 °C / Enzymatic reaction View Scheme
Multi-step reaction with 3 steps 1: Candida rugosa lipase / di-isopropyl ether; aq. phosphate buffer / 120 h / 40 °C / Enzymatic reaction 2: triethylamine; dmap / dichloromethane / 4 h / 0 °C 3: Candida rugosa lipase / di-isopropyl ether; aq. phosphate buffer / 120 h / 40 °C / pH 6.2 / Enzymatic reaction View Scheme

(R,S)-3-[5-(4-fluorophenyl)-5-hydroxy-pentanoyl]-4-phenyl-oxazolidin-2-one (1246853-48-4) → (R)-1-(4-fluorophenyl)-5-oxo-5-[(S)-2-oxo-4-phenyloxazolidin-3-yl]pentyl acetate (1246853-49-5) + (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: triethylamine; dmap / dichloromethane / 4 h / 0 °C 2: Candida rugosa lipase / di-isopropyl ether; aq. phosphate buffer / 120 h / 40 °C / pH 6.2 / Enzymatic reaction View Scheme

Benzyl acetate (140-11-4) + (R,S)-3-[5-(4-fluorophenyl)-5-hydroxy-pentanoyl]-4-phenyl-oxazolidin-2-one (1246853-48-4) → (R)-1-(4-fluorophenyl)-5-oxo-5-[(S)-2-oxo-4-phenyloxazolidin-3-yl]pentyl acetate (1246853-49-5) + (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3) + (4S)-3-[(5R)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidin-2-one

Conditions	Yield
With Candida antarctica B lipase In toluene at 35℃; for 120h; Solvent; Reagent/catalyst; Enzymatic reaction;	A n/a B n/a C n/a

vinyl acetate (108-05-4) + (R,S)-3-[5-(4-fluorophenyl)-5-hydroxy-pentanoyl]-4-phenyl-oxazolidin-2-one (1246853-48-4) → (R)-1-(4-fluorophenyl)-5-oxo-5-[(S)-2-oxo-4-phenyloxazolidin-3-yl]pentyl acetate (1246853-49-5) + (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3) + (4S)-3-[(5R)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidin-2-one

Conditions	Yield
With Candida antarctica B lipase In toluene at 35℃; for 120h; Solvent; Reagent/catalyst; Enzymatic reaction;	A n/a B n/a C n/a

(RS)-1-(4-fluorophenyl)-5-oxo-5-[(S)-2-oxo-4-phenyloxazolidin-3-yl]pentyl acetate → (R)-1-(4-fluorophenyl)-5-oxo-5-[(S)-2-oxo-4-phenyloxazolidin-3-yl]pentyl acetate (1246853-49-5) + (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3)

Conditions	Yield
With Candida rugosa lipase In aq. phosphate buffer; di-isopropyl ether at 40℃; for 120h; pH=6.2; Solvent; Reagent/catalyst; Temperature; pH-value; Concentration; Enzymatic reaction; enantioselective reaction;	A n/a B n/a

(S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione (189028-93-1) → (R)-1-(4-fluorophenyl)-5-oxo-5-[(S)-2-oxo-4-phenyloxazolidin-3-yl]pentyl acetate (1246853-49-5) + (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: borane-THF / dichloromethane / 6 h / 0 - 20 °C / Inert atmosphere 2: Candida rugosa lipase / di-isopropyl ether / 120 h / 35 °C / Enzymatic reaction View Scheme
Multi-step reaction with 3 steps 1: borane-THF / dichloromethane / 6 h / 0 - 20 °C / Inert atmosphere 2: triethylamine; dmap / dichloromethane / 4 h / 0 °C 3: Candida rugosa lipase / di-isopropyl ether; aq. phosphate buffer / 120 h / 40 °C / pH 6.2 / Enzymatic reaction View Scheme

(-)-6-(4-fluorophenyl)tetrahydro-2H-pyran-2-one (793673-93-5) → (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: dmap / 1,4-dioxane / 16 h / 55 - 60 °C 2: dmap; triethylamine / tetrahydrofuran / 2 h / 4 °C 3: sodium hydride / N,N-dimethyl-formamide / 2 h / 4 - 20 °C View Scheme

(5S)-5-(4-fluorophenyl)-5-hydroxy-N-((S)-2-hydroxy-1-phenylethyl)pentanamide → (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: dmap; triethylamine / tetrahydrofuran / 2 h / 4 °C 2: sodium hydride / N,N-dimethyl-formamide / 2 h / 4 - 20 °C View Scheme

tert-butyl (S)-5-(4-fluorophenyl)-5-hydroxypentanoyl((S)-2-hydroxy-1-phenylethyl)carbamate → (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide at 4 - 20℃; for 2h;	800 mg

5-(4-fluorophenyl)-5-oxopentanoic acid (149437-76-3) → (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: sulfuric acid / 1 h / Reflux 2.1: Pinene; sodium tetrahydroborate; boron trichloride / tetrahydrofuran; 1,2-dimethoxyethane; hexane / 16 h / -15 - 4 °C 2.2: 2 h / 4 - 20 °C 3.1: trifluoroacetic acid / dichloromethane / 3 h / 20 °C 4.1: dmap / 1,4-dioxane / 16 h / 55 - 60 °C 5.1: dmap; triethylamine / tetrahydrofuran / 2 h / 4 °C 6.1: sodium hydride / N,N-dimethyl-formamide / 2 h / 4 - 20 °C View Scheme
Multi-step reaction with 2 steps 1.1: triethylamine; pivaloyl chloride / dichloromethane / 2.5 h / 5 - 10 °C 1.2: 3 h / 15 - 45 °C 2.1: dimethylsulfide borane complex; (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole / tetrahydrofuran / 2.33 h / -10 - -5 °C 2.2: -10 - 0 °C View Scheme

fluorobenzene (462-06-6) → (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3)

Conditions

Yield

Multi-step reaction with 7 steps 1.1: aluminum (III) chloride / dichloromethane / 0.5 h / 0 °C 2.1: sulfuric acid / 1 h / Reflux 3.1: Pinene; sodium tetrahydroborate; boron trichloride / tetrahydrofuran; 1,2-dimethoxyethane; hexane / 16 h / -15 - 4 °C 3.2: 2 h / 4 - 20 °C 4.1: trifluoroacetic acid / dichloromethane / 3 h / 20 °C 5.1: dmap / 1,4-dioxane / 16 h / 55 - 60 °C 6.1: dmap; triethylamine / tetrahydrofuran / 2 h / 4 °C 7.1: sodium hydride / N,N-dimethyl-formamide / 2 h / 4 - 20 °C View Scheme

(S)-5-(4-fluorophenyl)-5-hydroxypentanoic acid → (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: trifluoroacetic acid / dichloromethane / 3 h / 20 °C 2: dmap / 1,4-dioxane / 16 h / 55 - 60 °C 3: dmap; triethylamine / tetrahydrofuran / 2 h / 4 °C 4: sodium hydride / N,N-dimethyl-formamide / 2 h / 4 - 20 °C View Scheme

glutaric anhydride, (108-55-4) → (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3)

Conditions

Yield

Multi-step reaction with 7 steps 1.1: aluminum (III) chloride / dichloromethane / 0.5 h / 0 °C 2.1: sulfuric acid / 1 h / Reflux 3.1: Pinene; sodium tetrahydroborate; boron trichloride / tetrahydrofuran; 1,2-dimethoxyethane; hexane / 16 h / -15 - 4 °C 3.2: 2 h / 4 - 20 °C 4.1: trifluoroacetic acid / dichloromethane / 3 h / 20 °C 5.1: dmap / 1,4-dioxane / 16 h / 55 - 60 °C 6.1: dmap; triethylamine / tetrahydrofuran / 2 h / 4 °C 7.1: sodium hydride / N,N-dimethyl-formamide / 2 h / 4 - 20 °C View Scheme

5-(4-fluorophenyl)-5-oxopentanoic acid methyl ester (149437-67-2) → (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: Pinene; sodium tetrahydroborate; boron trichloride / tetrahydrofuran; 1,2-dimethoxyethane; hexane / 16 h / -15 - 4 °C 1.2: 2 h / 4 - 20 °C 2.1: trifluoroacetic acid / dichloromethane / 3 h / 20 °C 3.1: dmap / 1,4-dioxane / 16 h / 55 - 60 °C 4.1: dmap; triethylamine / tetrahydrofuran / 2 h / 4 °C 5.1: sodium hydride / N,N-dimethyl-formamide / 2 h / 4 - 20 °C View Scheme

(S)-4-phenyl-2-oxazolidinone (99395-88-7) + 5-(4-fluorophenyl)-5-oxopentanoic acid (149437-76-3) → (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3)

Conditions	Yield
Stage #1: 5-(4-fluorophenyl)-5-oxopentanoic acid With pivaloyl chloride; triethylamine In dichloromethane at 0 - 20℃; for 4h; Stage #2: (S)-4-phenyl-2-oxazolidinone In N,N-dimethyl-formamide at 20℃; for 2h; Reflux; Stage #3: With dimethylsulfide borane complex; (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole In dichloromethane at 0 - 20℃; for 3h;

(S)-4-phenyl-2-oxazolidinone (99395-88-7) → (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: triethylamine; pivaloyl chloride / dichloromethane / 2.5 h / 5 - 10 °C 1.2: 3 h / 15 - 45 °C 2.1: dimethylsulfide borane complex; (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole / tetrahydrofuran / 2.33 h / -10 - -5 °C 2.2: -10 - 0 °C View Scheme

chloro-trimethyl-silane (75-77-4) + (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3) → (S)-3-((S)-5-(4-fluorophenyl)-5-((trimethylsilyl)oxy)-pentanoyl)-4-phenyloxazolidin-2-one

Conditions	Yield
With triethylamine In tert-butyl methyl ether; toluene at -10 - 20℃; Inert atmosphere;	95%
Stage #1: chloro-trimethyl-silane; (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one With N-ethyl-N,N-diisopropylamine In dichloromethane at -10℃; for 1.5h; Stage #2: With titanium tetrachloride
With N-ethyl-N,N-diisopropylamine In dichloromethane at -10℃;

4-benzyloxybenzylidene-N-(4-fluoro)phenylanisidine (70627-52-0) + (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3) → C40H36F2N2O5 (1185883-39-9)

Conditions	Yield
Stage #1: 4-benzyloxybenzylidene-N-(4-fluoro)phenylanisidine; (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one With N-ethyl-N,N-diisopropylamine In dichloromethane at -5℃; for 2h; Inert atmosphere; Stage #2: With titanium tetrachloride In dichloromethane at -30℃; for 2h; Inert atmosphere;	94%

chloro-trimethyl-silane (75-77-4) + 4-benzyloxybenzylidene-N-(4-fluoro)phenylanisidine (70627-52-0) + (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3) → C43H44F2N2O5Si

Conditions	Yield
Stage #1: chloro-trimethyl-silane; 4-benzyloxybenzylidene-N-(4-fluoro)phenylanisidine; (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one With N-ethyl-N,N-diisopropylamine In dichloromethane at -5 - 5℃; Inert atmosphere; Stage #2: With titanium tetrachloride In dichloromethane at -5 - 5℃; for 1h;	93%

chloro-trimethyl-silane (75-77-4) + N-(4-hydroxybenzylidene)-4-fluorobenzenamine (3382-63-6) + (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3) → (4S)-3-[(2R,5S)-5-(4-fluorophenyl)-2-[(S)-[(4-fluorophenyl)amino]({4-[(trimethylsilyl)oxy]phenyl})methyl]-5-[(trimethylsilyl)oxy]pentanoyl]-4-phenyl-1,3-oxazolidin-2-one (272778-12-8)

Conditions	Yield
Stage #1: chloro-trimethyl-silane; N-(4-hydroxybenzylidene)-4-fluorobenzenamine; (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one With N-ethyl-N,N-diisopropylamine In dichloromethane at -10 - 0℃; Inert atmosphere; Stage #2: With titanium tetrachloride In dichloromethane at -30 - -25℃; Inert atmosphere;	66.6%
With triethylamine In dichloromethane at -20℃; Reagent/catalyst; Solvent;

chloro-trimethyl-silane (75-77-4) + (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3) → (4S)-3-[(2R,5S)-5-(4-fluorophenyl)-2-[(S)-[(4-fluorophenyl)amino]({4-[(trimethylsilyl)oxy]phenyl})methyl]-5-[(trimethylsilyl)oxy]pentanoyl]-4-phenyl-1,3-oxazolidin-2-one (272778-12-8)

Conditions	Yield
Stage #1: (E)-(4-hydroxy-benzylidene)-(4-fluorophenyl)-amine; (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one With N-ethyl-N,N-diisopropylamine In dichloromethane at -10 - -5℃; Stage #2: chloro-trimethyl-silane In dichloromethane at -5℃; for 1.5h; Stage #3: With titanium tetrachloride In dichloromethane at -30 - -25℃; for 3h;	65%

chloro-trimethyl-silane (75-77-4) + N-(4-hydroxybenzylidene)-4-fluorobenzenamine (3382-63-6) + (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3) → C39H46F2N2O5Si2

Conditions	Yield
Stage #1: N-(4-hydroxybenzylidene)-4-fluorobenzenamine; (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one With N-ethyl-N,N-diisopropylamine In dichloromethane at -10 - -5℃; Stage #2: chloro-trimethyl-silane In dichloromethane at -5℃; for 1.5h; Stage #3: With N,O-bis-(trimethylsilyl)-acetamide; titanium tetrachloride more than 3 stages;	65%

N-(4-hydroxybenzylidene)-4-fluorobenzenamine (3382-63-6) + chloromethyl methyl ether (107-30-2) + (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3) → C37H38F2N2O7

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane at -20 - -10℃; for 1h; Temperature; Reagent/catalyst;	64.5%

tert-butyldimethylsilyl chloride (18162-48-6) + (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3) → C26H34FNO4Si (937798-07-7)

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In N,N-dimethyl-formamide at 80℃; Reagent/catalyst; Temperature;	62%
With 1H-imidazole In N,N-dimethyl-formamide at 20℃; for 1h;	42 g

4-benzyloxybenzylidene-N-(4-fluoro)phenylanisidine (70627-52-0) + (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3) → C40H36F2N2O5

Conditions	Yield
With titanium(IV) isopropylate; titanium tetrachloride; N-ethyl-N,N-diisopropylamine In dichloromethane at -30 - -20℃; for 5h;	60.9%

chloro-trimethyl-silane (75-77-4) + N,O-bis-(trimethylsilyl)-acetamide (10416-59-8) + N-(4-hydroxybenzylidene)-4-fluorobenzenamine (3382-63-6) + (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3) → (4S)-3-[(2R,5S)-5-(4-fluorophenyl)-2-[(S)-[(4-fluorophenyl)amino]({4-[(trimethylsilyl)oxy]phenyl})methyl]-5-[(trimethylsilyl)oxy]pentanoyl]-4-phenyl-1,3-oxazolidin-2-one (272778-12-8)

Conditions	Yield
Stage #1: chloro-trimethyl-silane; N-(4-hydroxybenzylidene)-4-fluorobenzenamine; (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one With N-ethyl-N,N-diisopropylamine In dichloromethane at -10 - -5℃; for 1h; Stage #2: With titanium tetrachloride In dichloromethane at -30℃; for 20h; Stage #3: N,O-bis-(trimethylsilyl)-acetamide	60%

N-{(1E)-[2-(benzyloxy)-4-bromophenyl]methylene}-N-phenylamine (914777-35-8) + (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3) → (S)-3-[(2R,5S)-2-[(S)-(2-benzyloxy-4-bromo-phenyl)-phenylamino-methyl]-5-(4-fluoro-phenyl)-5-hydroxy-pentanoyl]-4-phenyl-oxazolidin-2-one (914777-36-9)

Conditions	Yield
Stage #1: (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one With chloro-trimethyl-silane; N-ethyl-N,N-diisopropylamine In dichloromethane at -45 - -20℃; for 1h; Stage #2: With titanium tetrachloride In dichloromethane at -35 - -30℃; for 0.75h; Stage #3: N-{(1E)-[2-(benzyloxy)-4-bromophenyl]methylene}-N-phenylamine With acetic acid more than 3 stages;	51%
Stage #1: (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one With chloro-trimethyl-silane; N-ethyl-N,N-diisopropylamine In dichloromethane at -45 - -20℃; for 1h; Stage #2: With titanium tetrachloride In dichloromethane at -45 - -30℃; for 1.08333h; Stage #3: N-{(1E)-[2-(benzyloxy)-4-bromophenyl]methylene}-N-phenylamine With acetic acid; tartaric acid more than 3 stages;	51%

(4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3) + C10(13)C6H18FNOSi → C30(13)C6H38F2N2O5Si

Conditions	Yield
With titanium tetrachloride In dichloromethane at -35 - -30℃; for 3h;

(4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3) → 1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-hydroxypropyl]-4-([12C6]-4-hydroxyphenyl)-2-azetidinone

Conditions	Yield
Multi-step reaction with 3 steps 1.1: TiCl4 / CH2Cl2 / 3 h / -35 - -30 °C 2.1: 995 mg / CH2Cl2 / 0.5 h / Heating 3.1: BSA / CH2Cl2 / 0.25 h / 20 °C 3.2: TBAF*3H2O / CH2Cl2 / 90 h / 0 °C 3.3: 90 percent / aq. H2SO4 / propan-2-ol / 1 h View Scheme

(4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3) → C33(13)C6H46F2N2O5Si2 (438624-70-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: TiCl4 / CH2Cl2 / 3 h / -35 - -30 °C 2: 995 mg / CH2Cl2 / 0.5 h / Heating View Scheme

benzyl bromide (100-39-0) + (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3) → (4S)-3-[(5S)-5-(benzyloxy)-5-(4-fluorophenyl)pentanoyl]-4-phenyl-1,3-oxazolidin-2-one (851860-27-0)

Conditions	Yield
With sodium hydride In DMF (N,N-dimethyl-formamide) at 0 - 20℃; for 0.666667h;

chloro-trimethyl-silane (75-77-4) + 4-{[(1E)-(4-iodophenyl)methylene]amino}phenol (3230-41-9) + (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3) → C40H48FIN2O5Si2

Conditions	Yield
Stage #1: 4-{[(1E)-(4-iodophenyl)methylene]amino}phenol; (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one With N-ethyl-N,N-diisopropylamine In dichloromethane at -5 - 0℃; Stage #2: chloro-trimethyl-silane In dichloromethane at -25 - 0℃; for 1h; Stage #3: With titanium tetrachloride; sodium hydrogensulfite; rochelle salt more than 3 stages;

chloro-trimethyl-silane (75-77-4) + 4-({(1E)-[2-(allyloxy)-4-bromophenyl]methylene}amino)phenol (1078641-31-2) + (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3) → (4S)-3-{(2R,5S)-2-{(S)-[2-(allyloxy)-4-bromophenyl][(4-hydroxyphenyl)amino]methyl}-5-(4-fluorophenyl)-5-[(trimethylsilyl)oxy]pentanoyl}-4-phenyl-1,3-oxazolidin-2-one (1078641-32-3)

Conditions

Yield

Stage #1: chloro-trimethyl-silane; 4-({(1E)-[2-(allyloxy)-4-bromophenyl]methylene}amino)phenol; (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one With N-ethyl-N,N-diisopropylamine In dichloromethane at -30 - 0℃; for 1h; Stage #2: With Rochelle's salt; sodium hydrogensulfite; acetic acid; titanium tetrachloride In dichloromethane; water at -30 - 20℃; Cooling with ice/salt; Stage #3: With N,O-bis-(trimethylsilyl)-acetamide at 45℃; for 0.5h;

Reaxys ID: 19845323 + N-(4-hydroxybenzylidene)-4-fluorobenzenamine (3382-63-6) + (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3) → Reaxys ID: 19845322

Conditions	Yield
With titanium tetrachloride; N-ethyl-N,N-diisopropylamine In dichloromethane

(4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3) → ezetemibe (163222-33-1)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: N-ethyl-N,N-diisopropylamine / dichloromethane / -10 °C 2.1: titanium tetrachloride / dichloromethane / 0.75 h / -40 °C 2.2: 19.5 h / -40 - -35 °C 3.1: acetic acid / dichloromethane / 1 h 3.2: 1 h / 0 °C 3.3: 1 h / 20 °C 4.1: toluene / 3 h / 90 °C 4.2: 14 h / 50 °C 5.1: hydrogenchloride; water; acetic acid; iron / ethanol / 0.5 h / 0 - 20 °C 6.1: sodium nitrite; sulfuric acid / N,N-dimethyl-formamide; water / 1.5 h / 0 °C 6.2: 0.42 h / 20 - 90 °C View Scheme
Multi-step reaction with 2 steps 1.1: N-ethyl-N,N-diisopropylamine; chloro-trimethyl-silane; titanium tetrachloride / dichloromethane / 2 h / -30 - -25 °C 1.2: 2 h / Reflux 2.1: bis-(trimethylsilyl)acetamide; tetrabutyl ammonium fluoride / tert-butyl methyl ether / 1.5 h / 20 °C 2.2: 0.5 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / -20 °C 2: H-ZSM-5 molecular sieve / -30 °C 3: perchloric acid / 3 h / 40 °C View Scheme

(4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3) → C36H37F2N3O6Si

Conditions	Yield
Multi-step reaction with 2 steps 1.1: N-ethyl-N,N-diisopropylamine / dichloromethane / -10 °C 2.1: titanium tetrachloride / dichloromethane / 0.75 h / -40 °C 2.2: 19.5 h / -40 - -35 °C View Scheme

(4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3) → (4S)-phenyl-3-[(5S)-(4-fluorophenyl)-(2R)-[(1S)-(4-fluorophenylamino)-1-(4-nitrophenyl)methyl]-5-hydroxypentanoyl]oxazolidin-2-one (1354716-96-3)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: N-ethyl-N,N-diisopropylamine / dichloromethane / -10 °C 2.1: titanium tetrachloride / dichloromethane / 0.75 h / -40 °C 2.2: 19.5 h / -40 - -35 °C 3.1: acetic acid / dichloromethane / 1 h 3.2: 1 h / 0 °C 3.3: 1 h / 20 °C View Scheme

(4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3) → 1-(4-fluorophenyl)-(3R)-[(3S)-(4-fluorophenyl)-3-trimethylsilyloxypropyl]-(4S)-(4-nitrophenyl)azetidin-2-one (1354716-97-4)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: N-ethyl-N,N-diisopropylamine / dichloromethane / -10 °C 2.1: titanium tetrachloride / dichloromethane / 0.75 h / -40 °C 2.2: 19.5 h / -40 - -35 °C 3.1: acetic acid / dichloromethane / 1 h 3.2: 1 h / 0 °C 3.3: 1 h / 20 °C 4.1: toluene / 3 h / 90 °C 4.2: 14 h / 50 °C View Scheme

(4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one (189028-95-3) → (4S)-(4-aminophenyl)-1-(4-fluorophenyl)-(3R)-[(3S)-(4-fluorophenyl)-3-hydroxypropyl]azetidin-2-one (1354716-98-5)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: N-ethyl-N,N-diisopropylamine / dichloromethane / -10 °C 2.1: titanium tetrachloride / dichloromethane / 0.75 h / -40 °C 2.2: 19.5 h / -40 - -35 °C 3.1: acetic acid / dichloromethane / 1 h 3.2: 1 h / 0 °C 3.3: 1 h / 20 °C 4.1: toluene / 3 h / 90 °C 4.2: 14 h / 50 °C 5.1: hydrogenchloride; water; acetic acid; iron / ethanol / 0.5 h / 0 - 20 °C View Scheme

Upstream product

• 189028-93-1 (S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione 
• 1246853-48-4 (R,S)-3-[5-(4-fluorophenyl)-5-hydroxy-pentanoyl]-4-phenyl-oxazolidin-2-one 
• 140-11-4 Benzyl acetate 
• 108-05-4 vinyl acetate 
• 793673-93-5 (-)-6-(4-fluorophenyl)tetrahydro-2H-pyran-2-one 
• 149437-76-3 5-(4-fluorophenyl)-5-oxopentanoic acid 
• 462-06-6 fluorobenzene 
• 189028-94-2 (S)-5-(4-fluorophenyl)-5-hydroxypentanoic acid 
• 108-55-4 glutaric anhydride, 
• 149437-67-2 5-(4-fluorophenyl)-5-oxopentanoic acid methyl ester 
• 99395-88-7 (S)-4-phenyl-2-oxazolidinone 
• 67-63-0 isopropyl alcohol 

Downstream Products

• 438624-68-1 1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-hydroxypropyl]-4-([12C₆]-4-hydroxyphenyl)-2-azetidinone 
• 438624-70-5 C₃₃⁽¹³⁾C₆H₄₆F₂N₂O₅Si₂ 
• 851860-27-0 (4S)-3-[(5S)-5-(benzyloxy)-5-(4-fluorophenyl)pentanoyl]-4-phenyl-1,3-oxazolidin-2-one 
• 272778-12-8 (4S)-3-[(2R,5S)-5-(4-fluorophenyl)-2-[(S)-[(4-fluorophenyl)amino]({4-[(trimethylsilyl)oxy]phenyl})methyl]-5-[(trimethylsilyl)oxy]pentanoyl]-4-phenyl-1,3-oxazolidin-2-one 
• 914777-36-9 (S)-3-[(2R,5S)-2-[(S)-(2-benzyloxy-4-bromo-phenyl)-phenylamino-methyl]-5-(4-fluoro-phenyl)-5-hydroxy-pentanoyl]-4-phenyl-oxazolidin-2-one 
• 1078641-32-3 (4S)-3-{(2R,5S)-2-{(S)-[2-(allyloxy)-4-bromophenyl][(4-hydroxyphenyl)amino]methyl}-5-(4-fluorophenyl)-5-[(trimethylsilyl)oxy]pentanoyl}-4-phenyl-1,3-oxazolidin-2-one 
• 163222-33-1 ezetemibe 
• 1354716-96-3 (4S)-phenyl-3-[(5S)-(4-fluorophenyl)-(2R)-[(1S)-(4-fluorophenylamino)-1-(4-nitrophenyl)methyl]-5-hydroxypentanoyl]oxazolidin-2-one 
• 1354716-97-4 1-(4-fluorophenyl)-(3R)-[(3S)-(4-fluorophenyl)-3-trimethylsilyloxypropyl]-(4S)-(4-nitrophenyl)azetidin-2-one 
• 1354716-98-5 (4S)-(4-aminophenyl)-1-(4-fluorophenyl)-(3R)-[(3S)-(4-fluorophenyl)-3-hydroxypropyl]azetidin-2-one 
• 272778-13-9 (3R,4S)-1-(4-fluorophenyl)-3-((S)-3-(4-fluorophenyl)-3-(trimethylsilyloxy)propanyl)-4-(4-(trimethylsiloxy)phenyl)azetidinone 
• 1185883-39-9 C₄₀H₃₆F₂N₂O₅ 

Relevant articles and documents

Process for preparing Ezetimibe intermediate by an acid enhanced chemo- and enantioselective CBS catalyzed ketone reduction

The S alcohol in the benzylic position of compound 2, a key feature of a novel cholesterol lowering agent Ezetimibe, was introduced by the (R)-MeCBS catalyzed asymmetric carbonyl reduction of ketone 1 using borane tetrahydrofuran complex (BTHF) as the reducing agent. The chemo- and enantioselectivity was dramatically enhanced by using an acid as a scavenger of the stabilizer sodium borohydride present in the commercially supplied pure BTHF. The effect of the critical reaction parameters such as addition mode of reagent, temperature, acids as well as water content on the selectivity has been examined. This reaction has been successfully applied in the commercial process for the preparation of the key intermediate 2 for Ezetimibe.

Process for preparing Ezetimibe intermediate by enantioselective CBS catalyzed ketone reduction with BH3-DEA prepared in situ

The (S) alcohol in the benzylic position of compound 2, a key intermediate in the synthesis of the cholesterol lowering agent Ezetimibe, was introduced by the (R)-MeCBS catalyzed asymmetric carbonyl reduction of ketone 1 using borane diethylaniline complex (BDEA) as the reducing agent. The latter was prepared in situ from sodium borohydride (NaBH4), diethylaniline (DEA) and dimethylsulfate (DMSO4). BDEA prepared in situ offers considerable advantages from the industrialization standpoint (cost and stability on storage of the reagents) over commercial solutions of BH3-THF (BTHF) or BH3-DMS (BMS). The effect of critical reaction parameters such as addition mode of reagent, temperature, solvent, reaction quenching as well as LiCl addition on the selectivity has been examined. This reaction has been successfully applied in the process for the preparation of key intermediate 2 for Ezetimibe.

Synthesis method of cholesterol absorption selective inhibitor drug intermediate

The invention discloses a synthesis method of a cholesterol absorption selective inhibitor drug intermediate, and is characterized in that the synthesis method comprises the following steps of: dissolving a raw material ezetimibe intermediate (4S)-3-[5-(4-fluorophenyl)-1, 5-dioxopentyl]-4-phenyl-2-oxazolidinone in an organic solvent according to a proper proportion, adding a glucose aqueous solution into the system, rapidly stirring, adjusting the pH to a required value, adding enzyme and coenzyme to continue reaction, controlling the pH of the system in the reaction process until the reaction is finished, adjusting the pH to be acidic after the reaction is finished, extracting, washing with water, concentrating, and evaporating to dryness to remove the solvent, thereby obtaining an oily matter which is a target compound (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxyl valeryl]-4-phenyl-1, 3-oxazacyclopentane-2-ketone. The synthesis method of the cholesterol absorption selective inhibitor drug intermediate has the advantages of being environmentally friendly, high in yield and purity, simple in preparation process, high in economic profit and the like.

Ezetimibe intermediate and preparation method of ezetimibe

The invention relates to an ezetimibe intermediate and a preparation method of ezetimibe. The ezetimibe intermediate has a structure as represented by a formula (I). The preparation method comprises the following steps: providing a compound represented by a formula (II); subjecting the compound as shown in a formula (II) to an asymmetric catalytic hydrogenation reaction under the action of a P-BIAMH catalyst to prepare a compound shown as the formula (I), wherein the P-BIAMH catalyst has a structure as shown in a formula (A) which is described in the specification. In the formula (A), X and Yare halogen independently; R1 is H or a C1-9 alkyl group; R2 is a high-molecular polymer; and a fragment as described in the specification represents a diphosphorus ligand. The method has the advantages of high conversion rate and high safety, and is especially suitable for industrial production.

Crystal form of ezetimibe key intermediate and preparation method of crystal form

The invention provides a crystal form of an ezetimibe key intermediate and a preparation method of the crystal form. The invention relates to the crystal form of (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-2-oxazolidinone and a preparation method thereof. Specifically, the invention provides the crystal form of a compound represented as in a formula (1), and the characteristic diffraction peaks exist in an X-ray powder diffraction pattern at the following 2[theta] angles: 6.195+/-0.2 degrees, 7.640+/-0.2 degrees, 8.289+/-0.2 degrees, 12.847+/-0.2 degrees, 18.394+/-0.2 degrees,19.871+/-0.2 degrees, 21.548+/-0.2 degrees and 25.062+/-0.2 degrees.

According to booklet mai bu synthesis of intermediates method

The invention discloses a according to the method for synthesizing intermediate folds mai bu, comprises the following steps: in under the nitrogen atmosphere, of formula (2) compound are added to in tetrahydrofuran to obtain solution A, A the solution temperature to 5 °C to 10 °C, and to the solution of (-) - A dropping two different pine pinane base chlorine borane, stirring the reaction, after the reaction is finished to obtain solution B, the solution B cooling to - 20 °C to 0 °C, aqueous solution of [...], adjusting solution B of pH=5 - 8, the ethyl acetate extract adjusting pH of the solution B, evaporate ethyl acetate to obtain the residue C, to the remainder of the organic solvent is added in the C, standing, pouring the organic solvent, the residue obtained D, D to the residue in toluene is added to obtain solution E, heating and stirring solution after E, natural cooling, the solution is put into the freezing environment in E, filtering, drying formula (1) compound of the solid, the method is simple and easy, and the cost is low. The reaction is shown as follows:

according to folds Mai Bu and its intermediate synthesis method

The invention provides an Ezetimibe synthesis method comprising the following steps: (a) a compound (5) is subjected to asymmetric reduction reaction to obtain a compound (6), and the compound (6) and tert-butyldimethylsilyl chloride react in an organic solution under the action of alkali to obtain a compound (7); (b) the compound (7) and diisopropylethylamine are dissolved in the organic solution, titanium tetrachloride is added in the organic solution to react at 20-50 DEG C, and a compound (3) is added in the organic solution at minus 20 to minus 60 DEG C to react to obtain a compound (8); (c) the compound (8) and N,O-bis(trimethylsilyl) acetamide react in the organic solution at 20-80 DEG C, tetrabutylammonium fluoride trihydrate is added into the organic solution to react at 20-80 DEG C to obtain a compound (9); (d) the compound (9) is subjected to off-protection reaction to obtain Ezetimibe, wherein R is equal to TBS, Ac or COOCH2CCl3. The invention further provides an Ezetimibe intermediate and a preparation method thereof.

An improved process for preparing according to bookletmai Bu

The invention discloses an improved method for preparing ezetimibe. The method comprises the steps of chirally reducing metal hydride and boride by using a reducing agent; carrying out hydroxy ether protection and condensation reaction by using a one-pot method; and cyclizing, carrying out ether removal protection and the like. The improved method has the advantages that the operation is simple, the reaction selectivity and product stability are good, and the optical purity and yield of the product are high, so that the improved method is suitable for industrial production.

Synthetic method for ezetimibe intermediate

The invention discloses a synthetic method for an ezetimibe intermediate. The synthetic method comprises: by taking a compound I as a raw material, mixing the compound I with a reaction solution; under the action of an acid-binding agent, firstly activating the compound I by pivaloyl chloride; then coupling the compound with S-4-phenyl-2-oxazolidinone; then carrying out reduction reaction through (R)-2-mehtyl-CBS-oxazole borane; and then carrying out post-treatment to prepare (4S)-3-[(5S)-5-(4-fluorophenyl-5-hydroxyl valeryl)-4-phenyl-1,3- azacyclocyclopentane-2-(one) (II), wherein the formula is as shown in the description, and the reaction solution comprises tetrahydrofuran, chloroform, dioxane or dichloromethane. The synthetic method for the ezetimibe intermediate disclosed by the invention has the advantages of being simple to operate, short in synthetic line and relatively low in synthetic cost, and is suitable for large-scaled industrial production.

PROCESS FOR PREPARING EZETIMIBE INTERMEDIATE

The present invention refers to [...] which can inhibit the cholesterol absorption and are (ezetimibe) used in the manufacture of an intermediate manufacturing method relates to compounds of formula 4, a chelatable metal compounds, and metal of formula 2 in one direction so that at step low id id compound of formula 3 to the asymmetrically reducing according to including of the present invention manufacturing method, a method that of the prior art compared to compounds of formula 4 economically, purity can be produced: Said in formula, The X and Ph as defined during specification.