41162-19-0

Basic information

• Product Name: Dimethyl (2-oxo-4-phenylbutyl)phosphonate
• Synonyms: DIMETHYL (2-OXO-4-PHENYLBUTYL)PHOSPHONATE;Dimethyl(2-oxo-4-phenylbutyl)phosphonate85%;Dimethyl-(2-Oxo-4-Phemylbutyl) Phosphaonte;Dimethyl-(2-oxo-4-phenylbutyl)phosphonate, 98 %;DIMETHYL (2-OXO-4-PHENYLBUTYL)PHOSPHONATE, TECH., 85%;Dimethyl (2-oxo-4-Phenyl butyl)Phosphate;Dimethyl (2-oxo-4-phenylbutyl)phosphonate,85%,tech.;DiMethyl (2-Oxo-4-phenybutyl)phospate
• CAS NO: 41162-19-0
• Molecular Formula: C₁₂H₁₇O₄P
• Molecular Weight: 256.23
• Product Categories: Phenyls & Phenyl-Het;Phenyls & Phenyl-Het
• Mol File: 41162-19-0.mol
• Article Data: 33

Chemical Properties

• Melting Point: 120-122 ?C (0.5 MMHG)
• Boiling Point: 120-122 °C (0.5 mmHg)
• Flash Point: >110°C
• Appearance: clear yellow liquid
• Density: 1.152 g/cm³
• Vapor Pressure: 1.9E-05mmHg at 25°C
• Refractive Index: 1.494
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• Solubility: Chloroform (Sparingly), Methanol (Slightly)
• Stability: Hygroscopic
• CAS DataBase Reference: Dimethyl (2-oxo-4-phenylbutyl)phosphonate(CAS DataBase Reference)
• NIST Chemistry Reference: Dimethyl (2-oxo-4-phenylbutyl)phosphonate(41162-19-0)
• EPA Substance Registry System: Dimethyl (2-oxo-4-phenylbutyl)phosphonate(41162-19-0)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 24/25
• Hazardous Substances Data: 41162-19-0(Hazardous Substances Data)

Usage

Chemical Properties

clear yellow liquid

Uses

Dimethyl (2-Oxo-4-phenylbutyl)phosphonate (Bimatoprost Impurity 12) is an impurity of Bimatoprost (B386800), an antiglaucoma agent. Bimatoprost is also a synthetic prostamide; structurally related to prostaglandin F2α.

InChI:InChI=1/C12H17O4P/c1-15-17(14,16-2)10-12(13)9-8-11-6-4-3-5-7-11/h3-7H,8-10H2,1-2H3

Synthetic route

3-phenylpropanoic acid methyl ester (103-25-3) + dimethyl methane phosphonate (756-79-6) → dimethyl(2-oxo-4-phenylbutyl)phosphonate (41162-19-0)

Conditions	Yield
Stage #1: dimethyl methane phosphonate With n-butyllithium In tetrahydrofuran at -78℃; for 0.5h; Inert atmosphere; Stage #2: 3-phenylpropanoic acid methyl ester In tetrahydrofuran at -78℃; for 1h;	98%
With n-butyllithium In tetrahydrofuran at -78 - 0℃; Inert atmosphere;	98%
Stage #1: dimethyl methane phosphonate With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Stage #2: 3-phenylpropanoic acid methyl ester In tetrahydrofuran; hexane at -78 - 0℃;	97%

ethyl dihydrocinnamate (2021-28-5) + dimethyl methane phosphonate (756-79-6) → dimethyl(2-oxo-4-phenylbutyl)phosphonate (41162-19-0)

Conditions	Yield
With n-butyllithium; diisopropylamine In tetrahydrofuran at 5 - 20℃; Inert atmosphere;	95%
With n-butyllithium 1.) THF, -78 deg C, 15 min, 2.) THF, -78 deg C, 30 min; Multistep reaction;
With n-butyllithium In tetrahydrofuran; diethyl ether; hexane; water; acetic acid
Stage #1: dimethyl methane phosphonate With n-hexyllithium In tetrahydrofuran; hexane at -80℃; Inert atmosphere; Stage #2: ethyl dihydrocinnamate In tetrahydrofuran; hexane at 20℃; Inert atmosphere; Stage #3: With water In tetrahydrofuran; hexane at 20℃;
With n-butyllithium In tetrahydrofuran; hexane

argon + 1-iodo-4-phenylbutan-2-one (352276-27-8) → dimethyl(2-oxo-4-phenylbutyl)phosphonate (41162-19-0)

Conditions	Yield
With phosphorous acid trimethyl ester In acetonitrile	85%

1-iodo-4-phenylbutan-2-one (352276-27-8) + phosphorous acid trimethyl ester (121-45-9) → dimethyl(2-oxo-4-phenylbutyl)phosphonate (41162-19-0)

Conditions	Yield
In acetonitrile at 20℃; for 2.5h; Reflux; Inert atmosphere;	60%

dimethyl (2-oxopropyl)phosphonate (4202-14-6) + benzyl chloride (100-44-7) → dimethyl(2-oxo-4-phenylbutyl)phosphonate (41162-19-0)

Conditions	Yield
(i) NaH, THF, (ii) nBuLi, hexane, (iii) /BRN= 471308/; Multistep reaction;

(E)-3-phenylacrylic acid (140-10-3) → dimethyl(2-oxo-4-phenylbutyl)phosphonate (41162-19-0)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: H2 / 5 percent Pd/C / ethyl acetate 2.1: MeOH 3.1: N-BuLi / tetrahydrofuran / 0 °C 3.2: tetrahydrofuran View Scheme

3-Phenylpropionic acid (501-52-0) → dimethyl(2-oxo-4-phenylbutyl)phosphonate (41162-19-0)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: MeOH 2.1: N-BuLi / tetrahydrofuran / 0 °C 2.2: tetrahydrofuran View Scheme
Multi-step reaction with 2 steps 1: sulfuric acid 2: n-butyllithium / tetrahydrofuran View Scheme
Multi-step reaction with 2 steps 1.1: sulfuric acid / 2 h / Reflux 2.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 2.2: 1 h / -78 °C View Scheme
Multi-step reaction with 2 steps 1: sulfuric acid / 2 h / Reflux 2: n-butyllithium / tetrahydrofuran / -78 - 0 °C / Inert atmosphere View Scheme

4-Phenyl-2-butanone (2550-26-7) → dimethyl(2-oxo-4-phenylbutyl)phosphonate (41162-19-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: bromine / methanol / 2.83 h / -5 - 20 °C / Inert atmosphere 2: sodium iodide / acetone / 6 h / 20 °C / Inert atmosphere 3: acetonitrile / 2.5 h / 20 °C / Reflux; Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1: bromine / methanol / 4 h / 0 - 15 °C 2: sodium iodide / acetone / 12 h 3: acetonitrile / 3 h / 65 °C View Scheme
Multi-step reaction with 2 steps 1: bromine; acetic acid / methanol / Inert atmosphere 2: acetonitrile / 3 h / 65 °C / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1: iodine; copper(II) oxide / methanol; dichloromethane / 15 h / 42 °C / Inert atmosphere 2: acetonitrile / 3 h / 65 °C / Inert atmosphere View Scheme

1-bromo-4-phenylbutan-2-one (31984-10-8) → dimethyl(2-oxo-4-phenylbutyl)phosphonate (41162-19-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium iodide / acetone / 6 h / 20 °C / Inert atmosphere 2: acetonitrile / 2.5 h / 20 °C / Reflux; Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1: sodium iodide / acetone / 12 h 2: acetonitrile / 3 h / 65 °C View Scheme

trimethyl phosphite (512-56-1) + 1-iodo-4-phenylbutan-2-one (352276-27-8) → dimethyl(2-oxo-4-phenylbutyl)phosphonate (41162-19-0)

Conditions	Yield
In acetonitrile at 65℃; for 3h;	73 g
In acetonitrile at 65℃; for 3h; Inert atmosphere;

trimethyl phosphite (512-56-1) + 1-bromo-4-phenylbutan-2-one (31984-10-8) → dimethyl(2-oxo-4-phenylbutyl)phosphonate (41162-19-0)

Conditions	Yield
In acetonitrile at 65℃; for 3h; Inert atmosphere;	72 g

4-Phenyl-1-butene (768-56-9) → dimethyl(2-oxo-4-phenylbutyl)phosphonate (41162-19-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 20 °C / Cooling with ice 2: zinc(II) chloride / toluene / 4 h / 65 - 70 °C / Inert atmosphere 3: Jones reagent / acetone / 5 h / Cooling with ice View Scheme

(2-hydroxy-4-phenyl-butyl)-phosphonic acid dimethyl ester → dimethyl(2-oxo-4-phenylbutyl)phosphonate (41162-19-0)

Conditions	Yield
With Jones reagent In acetone for 5h; Cooling with ice;	15.8 g

(3aR,4R,5R,6aS)-5-((tert-butyldimethylsilyl)oxy)-2-oxohexahydro-2H-cyclopenta[b]furan-4-carbaldehyde (64091-14-1) + dimethyl(2-oxo-4-phenylbutyl)phosphonate (41162-19-0) → (3aR,4R,5R,6aS)-5-((tert-butyldimethylsilyl)oxy)-4-((E)-3-oxo-5-phenylpent-1-en-1-yl)hexahydro-2H-cyclopenta[b]furan-2-one (1240483-13-9)

Conditions	Yield
Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃; Inert atmosphere; Stage #2: (3aR,4R,5R,6aS)-5-((tert-butyldimethylsilyl)oxy)-2-oxohexahydro-2H-cyclopenta[b]furan-4-carbaldehyde In tetrahydrofuran; mineral oil at 0℃;	93%
With triethylamine; lithium chloride In acetonitrile for 2h; Inert atmosphere;	92%

(3aR,4R,5R,6aS)-5-((tert-butyldimethylsilyl)oxy)-2-oxohexahydro-2H-cyclopenta[b]furan-4-carbaldehyde (64091-14-1) + dimethyl(2-oxo-4-phenylbutyl)phosphonate (41162-19-0) → C24H34O4Si

Conditions	Yield
Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃; for 1h; Inert atmosphere; Stage #2: (3aR,4R,5R,6aS)-5-((tert-butyldimethylsilyl)oxy)-2-oxohexahydro-2H-cyclopenta[b]furan-4-carbaldehyde In tetrahydrofuran; mineral oil at 0℃; for 1.5h;	93%
Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With potassium carbonate In tetrahydrofuran at 20℃; for 1h; Inert atmosphere; Stage #2: (3aR,4R,5R,6aS)-5-((tert-butyldimethylsilyl)oxy)-2-oxohexahydro-2H-cyclopenta[b]furan-4-carbaldehyde In tetrahydrofuran at -20℃; Reagent/catalyst; Inert atmosphere;	86%

3-phenyl-propionaldehyde (104-53-0) + dimethyl(2-oxo-4-phenylbutyl)phosphonate (41162-19-0) → (4E)-1,7-diphenylhept-4-en-3-one (79559-59-4)

Conditions	Yield
Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With potassium carbonate In tetrahydrofuran at 20℃; for 0.666667h; Inert atmosphere; Stage #2: 3-phenyl-propionaldehyde at 40℃; for 12h;	92%
With potassium hexamethylsilazane Multistep reaction;

3-phenyl-propionaldehyde (104-53-0) + dimethyl(2-oxo-4-phenylbutyl)phosphonate (41162-19-0) → 1,7-diphenyl-4-heptene-3-one (79559-59-4)

Conditions	Yield
Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With potassium carbonate In tetrahydrofuran at 20℃; for 0.666667h; Inert atmosphere; Stage #2: 3-phenyl-propionaldehyde In tetrahydrofuran at 40℃; for 12h;	92%

dimethyl(2-oxo-4-phenylbutyl)phosphonate (41162-19-0) + (3aR,4R,5R,6aS)-4-formyl-2-oxohexahydro-2H-cyclopenta[b]furan-5-yl biphenyl-4-carboxylate (38754-71-1) → (1S,5R,6R,7R)-6-(3-oxo-5-phenyl-1E-pentenyl)-7-<(4-phenylbenzoyl)oxy>-2-oxabicyclo<3.3.0>octan-3-one (41639-72-9)

Conditions	Yield
Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With potassium carbonate In isopropyl alcohol at 25℃; for 0.5h; Horner-Wadsworth-Emmons Olefination; Stage #2: (3aR,4R,5R,6aS)-4-formyl-2-oxohexahydro-2H-cyclopenta[b]furan-5-yl biphenyl-4-carboxylate In isopropyl alcohol at 25℃; for 5h; Temperature; Horner-Wadsworth-Emmons Olefination;	91%
With N-ethyl-N,N-diisopropylamine; lithium chloride In acetonitrile at -15℃;	70%
With sodium hydride 1.) THF, 90 min, 2.) THF, 30 min; Multistep reaction;
With sodium hydroxide In dichloromethane; water at 0 - 5℃; for 1.5h; Product distribution / selectivity;

dimethyl(2-oxo-4-phenylbutyl)phosphonate (41162-19-0) + Corey aldehyde (62961-72-2) → (3aR,4R,5R,6aS)-5-hydroxy-4-((E)-3-oxo-5-phenylpent-1-en-1-yl)hexahydro-2H-cyclopenta[b]furan-2-one

Conditions	Yield
Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With potassium tert-butylate In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; Stage #2: Corey aldehyde In tetrahydrofuran at 20℃; for 6h; Reagent/catalyst; Temperature; Inert atmosphere;	88%
Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With sodium hydride In tetrahydrofuran at 0℃; for 1h; Inert atmosphere; Stage #2: Corey aldehyde In tetrahydrofuran at 0 - 20℃; for 6h; Inert atmosphere;

(S)-1-(2-oxoethyl)but-3-enyl acrylate + dimethyl(2-oxo-4-phenylbutyl)phosphonate (41162-19-0) → (4S,6E)-8-oxo-10-phenyldeca-1,6-dien-4-yl prop-2-enoate

Conditions	Yield
With sodium hexamethyldisilazane at 0℃; for 12h; Horner-Wadsworth-Emmons olefination;	87%

C8H13NO3 (1092078-92-6) + dimethyl(2-oxo-4-phenylbutyl)phosphonate (41162-19-0) → C18H23NO3 (1092078-93-7)

Conditions	Yield
Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With sodium hydride In tetrahydrofuran at 20℃; for 1h; Horner-Wadsworth-Emmons olefination; Stage #2: C8H13NO3 In tetrahydrofuran at 20℃; for 1h; Horner-Wadsworth-Emmons olefination;	86%

dimethyl(2-oxo-4-phenylbutyl)phosphonate (41162-19-0) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (3aR,4R,5R,6aS)-2-oxo-4-((1E)-3-oxo-5-phenylpent-1-en-1-yl)-hexahydro-2H-cyclopenta[b]furan-5-yl benzoate (55076-60-3)

Conditions	Yield
Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With N-ethyl-N,N-diisopropylamine; lithium chloride In acetonitrile at -15℃; Stage #2: (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one In acetonitrile at -15℃; Wittig Reaction;	84.7%
With triethylamine; lithium chloride In tetrahydrofuran; dichloromethane at 0℃; for 2h; Horner-Wadsworth-Emmons Olefination; Cooling with ice;	73%
Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With sodium hexamethyldisilazane In 1,2-dimethoxyethane Metallation; Stage #2: (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one In 1,2-dimethoxyethane Condensation;
With n-butyllithium In tetrahydrofuran; hexane; dichloromethane; acetic acid
With triethylamine; lithium chloride In dichloromethane at 0℃; for 2h; Horner-Emmons reaction;

dimethyl(2-oxo-4-phenylbutyl)phosphonate (41162-19-0) + 2,2-dihydroxyacetic acid (563-96-2) → (E)-4-oxo-6-phenylhex-2-enoic acid

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at -20℃; for 2h; Horner-Wadsworth-Emmons Olefination; stereoselective reaction;	83%

dimethyl(2-oxo-4-phenylbutyl)phosphonate (41162-19-0) + 2-dibenzylamino-5-oxo-pentanoic acid benzyl ester (850209-99-3) → (S,E)-benzyl 2-(dibenzylamino)-7-oxo-9-phenylnon-5-enoate (1379764-51-8)

Conditions	Yield
Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With N-ethyl-N,N-diisopropylamine; lithium chloride In acetonitrile at 20℃; Horner-Wadsworth-Emmons olefination; Inert atmosphere; Stage #2: 2-dibenzylamino-5-oxo-pentanoic acid benzyl ester In acetonitrile at 20℃; Horner-Wadsworth-Emmons olefination; Inert atmosphere;	80%

dimethyl(2-oxo-4-phenylbutyl)phosphonate (41162-19-0) + ethyl 2-((1R,2S,3R)-3-(dimethyl(phenyl)silyl)-2-formyl-5-oxocyclopentyl)acetate → ethyl 2-((1R,2R,3R)-3-(dimethyl(phenyl)silyl)-5-oxo-2-((E)-3-oxo-5-phenylpent-1-en-1-yl)cyclopentyl)acetate

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; lithium chloride In acetonitrile at 20℃; for 6h; Horner-Wadsworth-Emmons Olefination; Inert atmosphere;	73%

dimethyl(2-oxo-4-phenylbutyl)phosphonate (41162-19-0) + (3aR,4R,5R,6aS)-5-((tert-butyldiphenylsilyl)oxy)-2-oxohexahydro-2H-cyclopenta[b]furan-4-carbaldehyde → (3aR,4R,5R,6aS)-5-(tert-butyldiphenylsilyloxy)-4-((E)-3-oxo-5-phenylpent-1-enyl)hexahydro-2H-cyclopenta[b]furan-2-one (1395619-06-3)

Conditions	Yield
Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With triethylamine; lithium chloride In tetrahydrofuran at -10℃; for 1.5h; Horner-Wadsworth-Emmons Olefination; Inert atmosphere; Stage #2: (3aR,4R,5R,6aS)-5-((tert-butyldiphenylsilyl)oxy)-2-oxohexahydro-2H-cyclopenta[b]furan-4-carbaldehyde In tetrahydrofuran at -10℃; for 2.41667h; Inert atmosphere;	72%

C30H34O7 + dimethyl(2-oxo-4-phenylbutyl)phosphonate (41162-19-0) → 4-[(Z)-7-isopropoxy-7-oxohept-2-enyl]-5-[(E)-3-oxo-5-phenylpent-1-enyl]cyclopentane-1,3-diyl dibenzoate

Conditions	Yield
Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With sodium hydride In 1,2-dimethoxyethane at -5 - 25℃; Inert atmosphere; Stage #2: C30H34O7 In 1,2-dimethoxyethane at -5 - 25℃; Wittig reaction; Inert atmosphere;	70%

[(S)-2-(6-oxo-3,6-dihydro-2H-pyran-2-yl) acetaldehyde] + dimethyl(2-oxo-4-phenylbutyl)phosphonate (41162-19-0) + sodium hydride (7646-69-7) → (6R)-(4-oxo-6-phenyl-hex-2-enyl)-5,6-dihydro-pyran-2-one

Conditions	Yield
Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate; sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 0.166667h; Inert atmosphere; Stage #2: [(S)-2-(6-oxo-3,6-dihydro-2H-pyran-2-yl) acetaldehyde] In tetrahydrofuran; mineral oil at -78℃; for 1h; Inert atmosphere;	66%

[(3aR,4R,5R,6aS)-hexahydro-2-oxo-5-(phenylmethoxy)-2H-cyclopenta[b]furan-4-carboxaldehyde] (163074-98-4) + dimethyl(2-oxo-4-phenylbutyl)phosphonate (41162-19-0) → C25H26O4

Conditions	Yield
With triethylamine; lithium chloride In tetrahydrofuran at -18 - -10℃; for 25h; Horner-Wadsworth-Emmons Olefination;	65%

dimethyl(2-oxo-4-phenylbutyl)phosphonate (41162-19-0) + 2-(trimethylsilyl)phenyl trifluoromethanesulfonate (88284-48-4) → dimethyl 2-(3-phenylpropanoyl)benzylphosphonate (1170736-73-8)

Conditions	Yield
Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate; 2-(trimethylsilyl)phenyl trifluoromethanesulfonate With cesium fluoride In tetrahydrofuran at 60℃; for 67h; Inert atmosphere; Stage #2: With silica gel In tetrahydrofuran; ethyl acetate	65%

(Z)-4-formyl-5-(7-isopropoxy-7-oxohept-2-enyl)cyclopentane-1,3-diyl dibenzoate + dimethyl(2-oxo-4-phenylbutyl)phosphonate (41162-19-0) → 4-[(Z)-7-isopropoxy-7-oxohept-2-enyl]-5-[(E)-3-oxo-5-phenylpent-1-enyl]cyclopentane-1,3-diyl dibenzoate

Conditions	Yield
Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With sodium hydride In 1,2-dimethoxyethane at -5 - 25℃; for 1.25h; Wittig reaction; Inert atmosphere; Stage #2: (Z)-4-formyl-5-(7-isopropoxy-7-oxohept-2-enyl)cyclopentane-1,3-diyl dibenzoate In 1,2-dimethoxyethane at -5 - 25℃; for 2h; Wittig reaction; Inert atmosphere;	65%

dimethyl(2-oxo-4-phenylbutyl)phosphonate (41162-19-0) → (1-diazo-2-oxo-4-phenylbutyl)phosphonic acid dimethyl ester.

Conditions	Yield
With 4-toluenesulfonyl azide; potassium carbonate	63%

dimethyl(2-oxo-4-phenylbutyl)phosphonate (41162-19-0) + (-)-7α-triethylsilyloxy-6β-formyl-cis-2-oxabicyclo<3.3.0>octan-3-one (128948-10-7) → C24H34O4Si

Conditions	Yield
Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With triethylamine; lithium chloride In tetrahydrofuran at -15 - -5℃; Stage #2: (-)-7α-triethylsilyloxy-6β-formyl-cis-2-oxabicyclo<3.3.0>octan-3-one In tetrahydrofuran for 1h;	51%
Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With lithium hydroxide monohydrate In tert-butyl methyl ether at 20℃; for 1h; Stage #2: (-)-7α-triethylsilyloxy-6β-formyl-cis-2-oxabicyclo<3.3.0>octan-3-one In tert-butyl methyl ether; water at 5℃; for 0.916667h; Wittig-Horner Reaction;	27.5 g
With lithium hydroxide monohydrate In tert-butyl methyl ether at 5℃; for 0.75h; Wittig-Horner Reaction; Inert atmosphere;

ethyl trifluoroacetate, (383-63-1) + dimethyl(2-oxo-4-phenylbutyl)phosphonate (41162-19-0) + phenylmagnesium bromide (100-58-3) → (E)-6,6,6-trifluoro-1,5-diphenylhex-4-en-3-one + (Z)-6,6,6-trifluoro-1,5-diphenylhex-4-en-3-one

Conditions	Yield
Stage #1: ethyl trifluoroacetate,; phenylmagnesium bromide In diethyl ether; water at -80 - 0℃; for 2h; Inert atmosphere; Stage #2: dimethyl(2-oxo-4-phenylbutyl)phosphonate With triethylamine; lithium bromide In tetrahydrofuran; diethyl ether; water at 0 - 40℃; for 5.16h; Inert atmosphere;	A 51% B 4%

[(S)-2-(6-oxo-3,6-dihydro-2H-pyran-2-yl) acetaldehyde] + dimethyl(2-oxo-4-phenylbutyl)phosphonate (41162-19-0) → (6R)-(4-oxo-6-phenyl-hex-2-enyl)-5,6-dihydro-pyran-2-one

Conditions	Yield
With sodium hydride In tetrahydrofuran Horner-Wadsworth-Emmons reaction;	20%

dimethyl(2-oxo-4-phenylbutyl)phosphonate (41162-19-0) + methyl <1α,2α(Z),3α,4α>-7-<3-formyl-7-oxabicyclo<2.2.1>hept-2-yl>-5-heptenoate (104596-33-0) → (Z)-7-[(1S,2R,3S,4R)-3-((E)-3-Oxo-5-phenyl-pent-1-enyl)-7-oxa-bicyclo[2.2.1]hept-2-yl]-hept-5-enoic acid methyl ester

Conditions	Yield
With sodium hydride 1.) DME, 2.) 23 deg C; Multistep reaction;

dimethyl(2-oxo-4-phenylbutyl)phosphonate (41162-19-0) + <1α,2β(5Z),3β,4α>-7-<5,6-exo-epoxy-3-formyl-7-oxabicyclo<2.2.1>hept-2-yl>-5-heptenoic acid methyl ester → (Z)-7-[(1S,2S,4R,5R,6R,7S)-7-((E)-3-Oxo-5-phenyl-pent-1-enyl)-3,8-dioxa-tricyclo[3.2.1.02,4]oct-6-yl]-hept-5-enoic acid methyl ester

Conditions	Yield
With triethylamine; lithium bromide 1.) CH2Cl2, 25 deg C, 15 min, 2.) 25 deg C, overnight; Multistep reaction;

dimethyl(2-oxo-4-phenylbutyl)phosphonate (41162-19-0) + (Z)-7-((1R,2S,3R,5S)-3,5-Dihydroxy-2-hydroxymethyl-cyclopentyl)-hept-5-enoic acid isopropyl ester (177616-22-7) → 15-keto-17-phenyl-18,19,20-trinorprostaglandin F2α isopropyl ester (130209-77-7)

Conditions	Yield
With aluminium trichloride; 3 A molecular sieve; dihydrogen peroxide; N-ethyl-N,N-diisopropylamine; pyridinium chlorochromate; lithium chloride; phenylboronic acid Yield given. Multistep reaction;

Upstream product

• 512-56-1 trimethyl phosphite 
• 31984-10-8 1-bromo-4-phenylbutan-2-one 
• 768-56-9 4-Phenylbut-1-ene 
• 352276-27-8 1-iodo-4-phenylbutan-2-one 
• 121-45-9 phosphorous acid trimethyl ester 
• 2550-26-7 4-Phenyl-2-butanone 
• 501-52-0 3-Phenylpropionic acid 
• 140-10-3 (E)-3-phenylacrylic acid 
• 103-25-3 3-phenylpropanoic acid methyl ester 
• 756-79-6 dimethyl methane phosphonate 
• 2021-28-5 ethyl dihydrocinnamate 
• 4202-14-6 dimethyl (2-oxopropyl)phosphonate 
• 100-44-7 benzyl chloride 

Downstream Products

• 130209-77-7 15-keto-17-phenyl-18,19,20-trinorprostaglandin F_2α isopropyl ester 
• 130273-87-9 15β-hydroxy-17-phenyl-18,19,20-trinorprostaglandin F_2α isopropyl ester 
• 130209-76-6 15α-hydroxy-17-phenyl-18,19,20-trinorprostaglandin F_2α isopropyl ester 
• 177768-48-8 (Z)-7-{(1R,2R,3R,5S)-3,5-Dihydroxy-2-[(2S,3S)-3-((R)-1-hydroxy-3-phenyl-propyl)-oxiranyl]-cyclopentyl}-hept-5-enoic acid isopropyl ester 
• 177768-49-9 (Z)-7-{(1R,2R,3R,5S)-3,5-Dihydroxy-2-[(2R,3R)-3-((R)-1-hydroxy-3-phenyl-propyl)-oxiranyl]-cyclopentyl}-hept-5-enoic acid isopropyl ester 
• 65657-33-2 7-[2-(3-oxo-5-phenyl-1-trans-pentenyl)-4-oxo-3-thiazolidinyl]heptanoic acid 
• 933789-26-5 (3aR,4R,5R,6aS)-5-hydroxy-4-((E)-3-oxo-5-phenylpent-1-en-1-yl)hexahydro-2H-cyclopenta[b]furan-2-one 
• 1240483-13-9 (3aR,4R,5R,6aS)-5-((tert-butyldimethylsilyl)oxy)-4-((E)-3-oxo-5-phenylpent-1-en-1-yl)hexahydro-2H-cyclopenta[b]furan-2-one 
• 1098095-15-8 (6R)-6-[(2E)-4-oxo-6-phenylhex-2-en-1-yl]-5,6-dihydro-2H-pyran-2-one 
• 1225487-37-5 (6S)-5,6-dihydro-6-[(2E)-4-oxo-6-phenylhex-2-en-1-yl]-2H-pyran-2-one 
• 1395619-06-3 (3aR,4R,5R,6aS)-5-(tert-butyldiphenylsilyloxy)-4-((E)-3-oxo-5-phenylpent-1-enyl)hexahydro-2H-cyclopenta[b]furan-2-one 

Relevant articles and documents

Stereoselective Synthesis of Functionalized α-Amino Acids Isolated by Filtration

Crystallization-induced diastereomer transformation (CIDT) represents a highly appealing and convenient synthetic tool. Despite its numerous advantages, it remains rather rarely used due to its uncertain predictability to occur. Herein, we describe CIDT based on aza-Michael reactions of diversely functionalized (E)-3-acylacrylic acids. This method provides direct access to a broad variety of α-amino acid derivatives in excellent stereochemical purities.

Unsaturated ketone compound as well as preparation method and application thereof

The present invention relates to a novel GPR52 antagonist. Specifically, the invention relates to an unsaturated ketone compound, a pharmaceutically acceptable salt, a stereoisomer or a prodrug molecule thereof, and a method for preparing a pharmaceutical composition thereof. The invention further relates to the use of the GPR52 antagonist as an orphan G protein coupled receptor GPR52 antagonist,and further relates to the use of the GPR52 antagonist in the preparation of drugs for preventing and treating Huntington's disease.

Preparation method of beta-carboxyl phosphate

The invention provides a preparation method of beta-carboxyl phosphate. The preparation method comprises the following steps: carrying out regional selective ring-opening reaction on an epoxy compound and trialkyl phosphite to generate beta-carboxyl phosphate intermediate; and then oxidizing the beta-carboxyl phosphate intermediate to obtain the beta-carboxyl phosphate. The method is gentle in reaction condition and simple and convenient to operate without protection of an anhydrous solvent and oxygen, and is suitable for large-scale production. The beta-carboxyl phosphate synthesized by the preparation method can be used as an important intermediate synthesized by various misoprostols, such as travoprost, bimatoprost and tafluprost.