189028-93-1

Basic information

• Product Name: (4S)-3-[5-(4-Fluorophenyl)-1,5-dioxopenyl]-4-phenyl-2-oxazolidinone
• Synonyms: (4S)-4-Phenyl-3-[5-(4-fluorophenyl)-5-oxopentanoyl]-1,3-oxazolidin-2-one;(S)-3-[5-(4-Fluorophenyl)-1,5-dioxopentyl]-4-phenyloxazolidin-2-one;1-(4-Fluorophenyl)-5-[(4S)-2-oxo-4-phenyl-3-oxazolidinyl]-1,5-pentanedione;(S)-1-(4-fluorophenyl)-5- (2-oxo-4-phenyloxazolidin-3-yl) pentane-1,5-dione;(S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl);(S)-3-(5-(4-fluorophenyl)-5-oxophentanoyl)-4-phenyloxazolidin-2-one;(S)-4-Phenyl-3-[5-(4-fluorophenyl)-5-oxopentanoyl]-2-oxazolidinone;Ezetimibe Impurity 8
• CAS NO: 189028-93-1
• Molecular Formula: C₂₀H₁₈FNO₄
• Molecular Weight: 355.36
• EINECS: 1308068-626-2
• Product Categories: Intermediate of ezetimibe;Ezetimibe intermediates;Aromatics
• Mol File: 189028-93-1.mol
• Article Data: 11

Chemical Properties

• Melting Point: 90.0 to 94.0 °C
• Boiling Point: 568.4 °C at 760 mmHg
• Flash Point: 297.6 °C
• Appearance: /
• Density: 1.288 g/cm³
• Vapor Pressure: 6.19E-13mmHg at 25°C
• Refractive Index: 1.578
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: soluble in Acetone
• PKA: -3.11±0.40(Predicted)
• CAS DataBase Reference: (4S)-3-[5-(4-Fluorophenyl)-1,5-dioxopenyl]-4-phenyl-2-oxazolidinone(CAS DataBase Reference)
• NIST Chemistry Reference: (4S)-3-[5-(4-Fluorophenyl)-1,5-dioxopenyl]-4-phenyl-2-oxazolidinone(189028-93-1)
• EPA Substance Registry System: (4S)-3-[5-(4-Fluorophenyl)-1,5-dioxopenyl]-4-phenyl-2-oxazolidinone(189028-93-1)

Safety Data

• Hazardous Substances Data: 189028-93-1(Hazardous Substances Data)

Usage

Chemical Properties

Off-White Solid

Uses

3-[5-(1,5-Dioxo-5-(p-fluophenylpentyl]-4(S)-phenyl-2-oxazolidinone (cas# 189028-93-1) is a compound useful in organic synthesis.

InChI:InChI=1/C20H18FNO4/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/h1-3,5-6,9-12,17H,4,7-8,13H2/t17-/m1/s1

Synthetic route

((1-(4-fluorophenyl)vinyl)oxy)trimethylsilane (58518-77-7) + (4S)-3-(1-oxo-2-propen-1-yl)-4-phenyl-1,3-oxazolidin-2-one (259529-54-9) → (S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione (189028-93-1)

Conditions	Yield
With iodine In toluene at 40℃;	94%

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

Conditions	Yield
With pyridinium chlorochromate In dichloromethane at 40℃; for 2h;	91%

(S)-4-phenyl-2-oxazolidinone (99395-88-7) + 5-(4-fluorophenyl)-5-oxopentanoic acid (149437-76-3) → (S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione (189028-93-1)

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane	86%
Stage #1: 5-(4-fluorophenyl)-5-oxopentanoic acid With dmap; pivaloyl chloride In N,N-dimethyl-formamide at 2 - 20℃; for 1.5h; Stage #2: (S)-4-phenyl-2-oxazolidinone In N,N-dimethyl-formamide at 30 - 35℃; for 2h;	85.7%
Stage #1: 5-(4-fluorophenyl)-5-oxopentanoic acid With pivaloyl chloride; triethylamine In tetrahydrofuran at -10℃; for 4h; Evans Aldol Reaction; Inert atmosphere; Stage #2: (S)-4-phenyl-2-oxazolidinone With lithium chloride In tetrahydrofuran at 20℃; for 2h; Inert atmosphere;	85%

pivaloyl chloride (3282-30-2) + 5-(4-fluorophenyl)-5-oxopentanoic acid (149437-76-3) + (S)-5-phenyl-1,3-oxazolidine-2-one (186343-35-1) → (S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione (189028-93-1)

Conditions	Yield
Stage #1: pivaloyl chloride; 5-(4-fluorophenyl)-5-oxopentanoic acid With dmap In N,N-dimethyl-formamide at 2 - 20℃; for 1.5h; Stage #2: (S)-5-phenyl-1,3-oxazolidine-2-one With dmap In N,N-dimethyl-formamide at 30 - 35℃; for 2h;	85.7%

C16H19FO4 (1056188-47-6) + (S)-4-phenyl-2-oxazolidinone (99395-88-7) → (S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione (189028-93-1)

Conditions	Yield
Stage #1: C16H19FO4; (S)-4-phenyl-2-oxazolidinone With dmap In N,N-dimethyl-formamide for 7h; Heating / reflux; Stage #2: With sulfuric acid In water; N,N-dimethyl-formamide for 0.5h; Stage #3: With sodium hydrogencarbonate In water; N,N-dimethyl-formamide
With dmap In DMF (N,N-dimethyl-formamide) for 7h; Heating / reflux;

(S)-4-phenyl-2-oxazolidinone (99395-88-7) → (S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione (189028-93-1)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: chloro-trimethyl-silane / dichloromethane / 0.5 h / 0 - 10 °C 1.2: 2 h / 0 - 10 °C 1.3: 2 h / 0 - 20 °C 2.1: iodine / toluene / 40 °C View Scheme

C24H26FNO5 → (S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione (189028-93-1)

Conditions	Yield
Multi-step reaction with 3 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 3: pyridinium chlorochromate / dichloromethane / 2 h / 40 °C 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: Candida antarctica B lipase / toluene / 120 h / 35 °C / Enzymatic reaction 3: pyridinium chlorochromate / dichloromethane / 2 h / 40 °C View Scheme

C24H26FNO5 → (S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione (189028-93-1)

Conditions	Yield
Multi-step reaction with 3 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 3: pyridinium chlorochromate / dichloromethane / 2 h / 40 °C 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: Candida antarctica B lipase / toluene / 120 h / 35 °C / Enzymatic reaction 3: pyridinium chlorochromate / dichloromethane / 2 h / 40 °C View Scheme

(R,S)-3-[5-(4-fluorophenyl)-5-hydroxy-pentanoyl]-4-phenyl-oxazolidin-2-one (1246853-48-4) → (S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione (189028-93-1)

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

1-(4-fluorophenyl)ethanone (403-42-9) → (S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione (189028-93-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: triethylamine / N,N-dimethyl-formamide / 10 h / 100 °C / Inert atmosphere 2: iodine / toluene / 40 °C View Scheme

fluorobenzene (462-06-6) → (S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione (189028-93-1)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: aluminum (III) chloride / 5 h / 15 - 30 °C 1.2: 0 - 20 °C 2.1: triethylamine; pivaloyl chloride / dichloromethane 2.2: 13 h / Reflux View Scheme

glutaric anhydride, (108-55-4) → (S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione (189028-93-1)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: aluminum (III) chloride / 5 h / 15 - 30 °C 1.2: 0 - 20 °C 2.1: triethylamine; pivaloyl chloride / dichloromethane 2.2: 13 h / Reflux View Scheme

trimethylsilyl cyanide (7677-24-9) + (S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione (189028-93-1) → 2-(4-fluorophenyl)-6-oxo-6-(2-oxo-4(S)-phenyloxazolidin-3-yl)-2-trimethylsilyloxyhexanenitrile (1232148-22-9)

Conditions	Yield
With iodine In dichloromethane at 0℃; for 2.33333h;	100%

(S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione (189028-93-1) + trimethyl orthoformate (149-73-5) → (S)-3-(5-(4-fluorophenyl)-5,5-dimethoxypentanoyl)-4-phenyloxazolidin-2-one (1185883-41-3)

Conditions	Yield
toluene-4-sulfonic acid In methanol Reflux;	99.02%
With sulfuric acid In methanol for 1.5h; Reflux;	80%
toluene-4-sulfonic acid In methanol at 20℃; Reflux;
With toluene-4-sulfonic acid at 20℃; for 23h; Reflux;

(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%

ethylene glycol (107-21-1) + (S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione (189028-93-1) → (S)-3-{4-[2-(4-fluorophenyl)dioxolan-2-yl]butanoyl}-4-phenyl-oxazolidin-2-one (942485-56-5)

Conditions	Yield
Stage #1: ethylene glycol; (S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione; chloro-trimethyl-silane at 20 - 25℃; for 20h; Stage #2: With water; sodium hydrogencarbonate In toluene at 50℃; for 0.5h; Product distribution / selectivity;	95%
With N-Bromosuccinimide; trimethyl orthoformate at 70℃; for 8h; Inert atmosphere;	95%
Stage #1: ethylene glycol; (S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione With toluene-4-sulfonic acid In toluene for 20 - 24h; Heating / reflux; Stage #2: With water; sodium carbonate In toluene at 50℃; Product distribution / selectivity;	94.9%

methanol (67-56-1) + (S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione (189028-93-1) → (S)-3-(5-(4-fluorophenyl)-5,5-dimethoxypentanoyl)-4-phenyloxazolidin-2-one (1185883-41-3)

Conditions	Yield
With N-Bromosuccinimide; trimethyl orthoformate at 50℃; for 9h; Inert atmosphere;	91%

2,2-Dimethyl-1,3-propanediol (126-30-7) + (S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione (189028-93-1) → 3-{4-[2-(4-fluorophenyl)-5,5-dimethyl-[1,3]dioxin-2-yl]butyryl}(4S)-phenyl-1,3-oxazolidin-2-one (953805-20-4)

Conditions	Yield
With phosphorus pentoxide; sulfuric acid In dichloromethane for 5h; Reflux;	89%
With Pyridine hydrobromide In toluene at 20 - 115℃; for 5h; Product distribution / selectivity;
With chloro-trimethyl-silane In dichloromethane at 20 - 115℃; for 5h; Product distribution / selectivity;

2,2,7,7-tetramethyl-3,6-dioxa-2,7-disilaoctane (7381-30-8) + (S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione (189028-93-1) → (S)-3-{4-[2-(4-fluorophenyl)dioxolan-2-yl]butanoyl}-4-phenyl-oxazolidin-2-one (942485-56-5)

Conditions	Yield
Stage #1: 2,2,7,7-tetramethyl-3,6-dioxa-2,7-disilaoctane; (S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione With trimethylsilyl trifluoromethanesulfonate In toluene at 20 - 50℃; for 3 - 4h; Stage #2: With water; sodium hydrogencarbonate In toluene Product distribution / selectivity;	89%

(S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione (189028-93-1) + trimethyleneglycol (504-63-2) → (S)-3-[4-[2-(4-fluorophenyl)-[1,3]dioxan-2-yl]-1-oxobutyl]-4-phenyloxazolidin-2-one (1056460-25-3)

Conditions	Yield
With N-Bromosuccinimide; trimethyl orthoformate at 100℃; for 12h; Inert atmosphere;	86.8%

(S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione (189028-93-1) → (R,S)-3-[5-(4-fluorophenyl)-5-hydroxy-pentanoyl]-4-phenyl-oxazolidin-2-one (1246853-48-4)

Conditions	Yield
With borane-THF In dichloromethane at 0 - 20℃; for 6h; Inert atmosphere;	70%

(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) → 1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-hydroxypropyl]-4-([12C6]-4-hydroxyphenyl)-2-azetidinone

Conditions	Yield
Multi-step reaction with 4 steps 1.1: (R)-(CH2)3CHCPh2O(B-Me)N; BH3*SMe2 / CH2Cl2 / 2 h / 0 °C 2.1: TiCl4 / CH2Cl2 / 3 h / -35 - -30 °C 3.1: 995 mg / CH2Cl2 / 0.5 h / Heating 4.1: BSA / CH2Cl2 / 0.25 h / 20 °C 4.2: TBAF*3H2O / CH2Cl2 / 90 h / 0 °C 4.3: 90 percent / aq. H2SO4 / propan-2-ol / 1 h View Scheme

(S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione (189028-93-1) → C30(13)C6H38F2N2O5Si

Conditions	Yield
Multi-step reaction with 2 steps 1: (R)-(CH2)3CHCPh2O(B-Me)N; BH3*SMe2 / CH2Cl2 / 2 h / 0 °C 2: TiCl4 / CH2Cl2 / 3 h / -35 - -30 °C View Scheme

(S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione (189028-93-1) → C33(13)C6H46F2N2O5Si2 (438624-70-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: (R)-(CH2)3CHCPh2O(B-Me)N; BH3*SMe2 / CH2Cl2 / 2 h / 0 °C 2: TiCl4 / CH2Cl2 / 3 h / -35 - -30 °C 3: 995 mg / CH2Cl2 / 0.5 h / Heating View Scheme

(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)

hydroxylamine hydrochloride (5470-11-1) + (S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione (189028-93-1) → (S)-3-(5-(4-fluorophenyl)-5-(hydroxyimino)pentanoyl)-4-phenyloxazolidin-2-one

Conditions	Yield
With potassium carbonate In isopropyl alcohol for 2 - 4h; Reflux;

N-methoxylamine hydrochloride (593-56-6) + (S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione (189028-93-1) → C21H21FN2O4 (1246611-03-9)

Conditions	Yield
With triethylamine In ethanol at 80 - 85℃; for 10h;

(S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione (189028-93-1) → C41H34F2N2O7 (1185883-42-4)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: toluene-4-sulfonic acid / 23 h / 20 °C / Reflux 2.1: dichloromethane; toluene / 0.83 h / -33 - -30 °C 2.2: 3.5 h / -33 °C 3.1: acetic acid; sodium dihydrogencitrate / dichloromethane; toluene / 0.58 h / -33 °C View Scheme

(S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione (189028-93-1) → C41H36F2N2O7 (1185883-38-8)

Conditions

Yield

Multi-step reaction with 4 steps 1.1: toluene-4-sulfonic acid / 23 h / 20 °C / Reflux 2.1: dichloromethane; toluene / 0.83 h / -33 - -30 °C 2.2: 3.5 h / -33 °C 3.1: acetic acid; sodium dihydrogencitrate / dichloromethane; toluene / 0.58 h / -33 °C 4.1: (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole / tetrahydrofuran / 0.17 h / 20 °C / Inert atmosphere 4.2: 1.67 h / Inert atmosphere 4.3: 0.17 h View Scheme

(S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione (189028-93-1) → C43H40F2N2O8

Conditions	Yield
Multi-step reaction with 2 steps 1.1: toluene-4-sulfonic acid / 23 h / 20 °C / Reflux 2.1: dichloromethane; toluene / 0.83 h / -33 - -30 °C 2.2: 3.5 h / -33 °C View Scheme

(S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione (189028-93-1) → (3R,4S)-4-[4-(benzyloxy)phenyl]-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-oxopropyl]azetidin-2-one (190595-65-4)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: hydroxylamine hydrochloride / pyridine / 0 - 20 °C 2.1: titanium(IV) isopropylate; N-ethyl-N,N-diisopropylamine; titanium tetrachloride / dichloromethane / 0 °C 2.2: -15 °C 3.1: N,O-bis-(trimethylsilyl)-acetamide / toluene / 0.5 h / 60 °C 3.2: 8 h / 60 °C 3.3: 20 h / 20 °C 4.1: hydrogenchloride; formaldehyd / water; tetrahydrofuran / 6 h / 20 °C View Scheme
Multi-step reaction with 5 steps 1.1: hydroxylamine hydrochloride / pyridine / 0 - 20 °C 2.1: dmap; 1H-imidazole / dichloromethane / 0.17 h / 20 °C 2.2: 5 h 3.1: titanium(IV) isopropylate; N-ethyl-N,N-diisopropylamine; titanium tetrachloride / dichloromethane / 0 °C 3.2: 3 h / -15 °C 4.1: N,O-bis-(trimethylsilyl)-acetamide / toluene / 0.5 h / 60 °C 4.2: 8 h / 60 °C 5.1: hydrogenchloride; formaldehyd / water; tetrahydrofuran / 4 h / 20 °C View Scheme
Multi-step reaction with 4 steps 1: phosphorus pentoxide; sulfuric acid / dichloromethane / 5 h / Reflux 2: N-ethyl-N,N-diisopropylamine; titanium(IV) isopropylate; titanium tetrachloride / dichloromethane / 3 h / -5 °C 3: N,O-Bis(trimethylsilyl)acetamide; tetrabutyl ammonium fluoride / toluene / 48 h / Reflux 4: formic acid / dichloromethane / 12 h / Reflux View Scheme
Multi-step reaction with 2 steps 1: toluene-4-sulfonic acid / hexane / 6 h / 25 °C 2: N,O-bis-(trimethylsilyl)-acetamide; tetrabutyl ammonium fluoride / toluene / 60 °C View Scheme

(S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione (189028-93-1) → (S)-3-(5-(4-fluorophenyl)-5-(hydroxyimino)pentanoyl)-4-phenyloxazolidin-2-one

Conditions	Yield
Stage #1: (S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione With hydroxylamine hydrochloride In pyridine at 0 - 20℃; Stage #2: With hydrogenchloride In water; ethyl acetate Product distribution / selectivity;

(S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione (189028-93-1) → (S)-3-((S)-2-((S)-(4-(benzyloxy)phenyl)(4-fluorophenylamino)methyl)-5-(tert-butyldimethylsilyloxyimino)-5-(4-fluorophenyl)pentanoyl)-4-phenyloxazolidin-2-one

Conditions	Yield
Multi-step reaction with 3 steps 1.1: hydroxylamine hydrochloride / pyridine / 0 - 20 °C 2.1: dmap; 1H-imidazole / dichloromethane / 0.17 h / 20 °C 2.2: 5 h 3.1: titanium(IV) isopropylate; N-ethyl-N,N-diisopropylamine; titanium tetrachloride / dichloromethane / 0 °C 3.2: 3 h / -15 °C View Scheme

Upstream product

• 99395-88-7 (S)-4-phenyl-2-oxazolidinone 
• 108-55-4 glutaric anhydride, 
• 462-06-6 fluorobenzene 
• 58518-77-7 ((1-(4-fluorophenyl)vinyl)oxy)trimethylsilane 
• 259529-54-9 (4S)-3-(1-oxo-2-propen-1-yl)-4-phenyl-1,3-oxazolidin-2-one 
• 403-42-9 1-(4-fluorophenyl)ethanone 
• 528565-93-7 (4S)-3-[(5R)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidin-2-one 
• 1246853-48-4 (R,S)-3-[5-(4-fluorophenyl)-5-hydroxy-pentanoyl]-4-phenyl-oxazolidin-2-one 
• 149437-76-3 5-(4-fluorophenyl)-5-oxopentanoic acid 
• 3282-30-2 pivaloyl chloride 
• 186343-35-1 (S)-5-phenyl-1,3-oxazolidine-2-one 
• 1056188-47-6 C₁₆H₁₉FO₄ 

Downstream Products

• 189028-95-3 (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one 
• 528565-93-7 (4S)-3-[(5R)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidin-2-one 
• 942485-56-5 (S)-3-{4-[2-(4-fluorophenyl)dioxolan-2-yl]butanoyl}-4-phenyl-oxazolidin-2-one 
• 1232148-22-9 2-(4-fluorophenyl)-6-oxo-6-(2-oxo-4(S)-phenyloxazolidin-3-yl)-2-trimethylsilyloxyhexanenitrile 
• 1246853-49-5 (R)-1-(4-fluorophenyl)-5-oxo-5-[(S)-2-oxo-4-phenyloxazolidin-3-yl]pentyl acetate 
• 1246853-48-4 (R,S)-3-[5-(4-fluorophenyl)-5-hydroxy-pentanoyl]-4-phenyl-oxazolidin-2-one 
• 937798-07-7 C₂₆H₃₄FNO₄Si 
• 795306-57-9 3′-(S)-4-(S)-3-(R)-[3′-t-butyldimethylsilyloxy-3′-(4-fluorophenyl)propyl]-4-(4-hydroxyphenyl)-1-(4-fluorophenyl)azetidin-2-one 
• 1004520-48-2 (3R,4S)-1-(4-fluorophenyl)-3-((S)-3-(4-fluorophenyl)-3-hydroxypropyl)-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)azetidin-2-one 
• 163222-33-1 ezetemibe 
• 163222-32-0 (3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone 
• 953805-24-8 4(S)-(4-benzyloxyphenyl)-1-(4-fluorophenyl)-3(R)-{2-[2-(4-fluorophenyI)-5,5-dimethyl-[1,3]-dioxan-2-yl]-ethyl}azetidine-2-one 
• 953805-22-6 3-{(2R,3S)-3-[(4-fluorophenyl)amino]-2-[2-(4-fluorophenyl)-5,5-dimethyl-1,3-dioxan-2-yl]-3-[4-(benzyloxy)phenyI]propanoyl}-(4S)-4-phenyl-1,3-oxazolidin-2-one 
• 191330-56-0 [14C]-Sch 57871 

Relevant articles and documents

Ezetimibe intermediate and preparation method of ezetimibe

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according to folds Mai Bu and its intermediate synthesis method

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