183905-31-9

Basic information

• Product Name: AcetaMide, N-[(2S)-2-(acetyloxy)-3-chloropropyl]-
• Synonyms: AcetaMide, N-[(2S)-2-(acetyloxy)-3-chloropropyl]-;(S)-1-[(Acetylamino)methyl]-2-chloroethyl acetate;(S)-Acetic acid 2-acetylamino-1-chloromethylethyl ester;(S)-N-[2-(Acetyloxy)-3-chloropropyl]acetamide;N-[(2S)-2-(Acetyloxy)-3-chloropropyl]acetamide;N-[(2S)-2-Acetoxy-3-chloropropyl]acetamide;(S)-1-AcetaMido-3-chloropropan-2-yl acetate;N-[(2S)-2-(acetyloxy)-3-chloropropyl]-
• CAS NO: 183905-31-9
• Molecular Formula: C₇H₁₂ClNO₃
• Molecular Weight: 193.62808
• EINECS: 1806241-263-5
• Mol File: 183905-31-9.mol
• Article Data: 13

Chemical Properties

• Boiling Point: 370.249 °C at 760 mmHg
• Flash Point: 177.721 °C
• Appearance: /
• Density: 1.171
• Storage Temp.: Keep in dark place,Inert atmosphere,Store in freezer, under -20°C
• PKA: 15.42±0.46(Predicted)
• CAS DataBase Reference: AcetaMide, N-[(2S)-2-(acetyloxy)-3-chloropropyl]-(CAS DataBase Reference)
• NIST Chemistry Reference: AcetaMide, N-[(2S)-2-(acetyloxy)-3-chloropropyl]-(183905-31-9)
• EPA Substance Registry System: AcetaMide, N-[(2S)-2-(acetyloxy)-3-chloropropyl]-(183905-31-9)

Safety Data

• Hazardous Substances Data: 183905-31-9(Hazardous Substances Data)

Usage

Chemical Properties

White crystals

Synthetic route

acetic anhydride (108-24-7) + (S)-1-amino-3-chloropropan-2-ol (53494-57-8) → N-[(2S)-2-acetoxy-3-chloropropyl]acetamide (183905-31-9)

Conditions	Yield
With triethylamine at 0 - 20℃; for 4h;	98%
With pyridine In tetrahydrofuran at 35 - 45℃; for 12h;

(S)-1-amino-3-chloro-2-propanol hydrochloride + acetic anhydride (108-24-7) → N-[(2S)-2-acetoxy-3-chloropropyl]acetamide (183905-31-9)

Conditions	Yield
With pyridine In dichloromethane at 30℃; for 20h;	90.6%

acetic anhydride (108-24-7) + (2S)-1-amino-3-chloropropan-2-ol hydrogen chloride → N-[(2S)-2-acetoxy-3-chloropropyl]acetamide (183905-31-9)

Conditions	Yield
With pyridine In dichloromethane at 20 - 40℃; for 22h;	89%
With pyridine In dichloromethane at 18 - 40℃; for 5h;	75%
With pyridine at 20℃;	47.98%

(S)-1-amino-3-chloro-2-propanol hydrochloride + acetyl chloride (75-36-5) → N-[(2S)-2-acetoxy-3-chloropropyl]acetamide (183905-31-9)

Conditions	Yield
With pyridine In dichloromethane at 0 - 20℃; for 10h;	86.1%

acetic anhydride (108-24-7) + (2S)-1-amino-3-chloropropan-2-ol hydrogen chloride → (1S)-2-{acetyl[(2S)-2-(acetyloxy)-3-chloropropyl]amino}-1-(chloromethyl)ethyl acetate + (1S)-2-{bis[(2S)-2-(acetyloxy)-3-chloropropyl]amino}-1-(chloromethyl)ethyl acetate + N-[(2S)-2-acetoxy-3-chloropropyl]acetamide (183905-31-9)

Conditions	Yield
With pyridine In dichloromethane for 19h; Time; Temperature;	A n/a B 0.27% C 82.9%

(S)-N-[[3-[3-fluoro-4-[4-morpholinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]amine (168828-90-8) + N-[(2S)-2-acetoxy-3-chloropropyl]acetamide (183905-31-9) → (R)-1-acetamido-3-((((S)-3-(3-fluoro-4-morpholinophenyl)-2-oxooxazolidin-5-yl)methyl)amino)propan-2-yl acetate

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 2h;	97.9%

[4-(3-oxo-morpholin-4-yl)phenyl]carbamic acid benzyl ester (1313613-18-1) + N-[(2S)-2-acetoxy-3-chloropropyl]acetamide (183905-31-9) → (S)-N-[{3-(4-(3-oxomorpholin-4-yl)phenyl)-2-oxo-1,3-oxazolidin-5-yl}methyl]acetamide (1429334-00-8)

Conditions	Yield
With lithium tert-butoxide In dichloromethane; N,N-dimethyl-formamide for 10h; Reagent/catalyst; Reflux;	93%

N-ethoxycarbonyl-3-fluoro-4-morpholinyl aniline (565176-83-2) + N-[(2S)-2-acetoxy-3-chloropropyl]acetamide (183905-31-9) → linezolid (165800-03-3)

Conditions	Yield
With lithium; tert-butyl alcohol In tetrahydrofuran; N,N-dimethyl acetamide; isopropyl alcohol at 0 - 20℃; Reagent/catalyst; Solvent; Concentration;	90.3%

N-[(2S)-2-acetoxy-3-chloropropyl]acetamide (183905-31-9) → N-[(2S)oxiranylmethyl]acetamide (183805-10-9)

Conditions	Yield
With potassium carbonate In methanol for 2h; Ambient temperature;	89%

(1-fluoro-5-oxo-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)-carbamic acid ethyl ester (741721-41-5) + N-[(2S)-2-acetoxy-3-chloropropyl]acetamide (183905-31-9) → (S)-N-[3-(1-fluoro-5-oxo-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)-2-oxo-oxazolidin-5-ylmethyl]-acetamide (741721-36-8)

Conditions	Yield
Stage #1: (1-fluoro-5-oxo-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)-carbamic acid ethyl ester With methanol; lithium tert-butoxide In DMF (N,N-dimethyl-formamide); hexane at 20℃; for 3.5h; Stage #2: N-[(2S)-2-acetoxy-3-chloropropyl]acetamide In DMF (N,N-dimethyl-formamide); hexane at 20℃; for 18.5h;	88%
With lithium tert-butoxide In hexane; N,N-dimethyl-formamide

benzyl-carbamic acid benzyl ester (39896-97-4) + N-[(2S)-2-acetoxy-3-chloropropyl]acetamide (183905-31-9) → C13H16N2O3

Conditions	Yield
Stage #1: benzyl-carbamic acid benzyl ester With lithium tert-butoxide In tetrahydrofuran at 20℃; for 0.5h; Stage #2: N-[(2S)-2-acetoxy-3-chloropropyl]acetamide In tetrahydrofuran; methanol at 10 - 25℃; for 15.5h;	82.7%

(4-bromo-3-fluoro-phenyl)-carbamic acid methyl ester (396076-65-6) + N-[(2S)-2-acetoxy-3-chloropropyl]acetamide (183905-31-9) → (5S)-N-[[3-(3-fluoro-4-bromophenyl)-2-oxo-oxazolidin-5-yl]methyl]acetamide (856677-05-9)

Conditions	Yield
Stage #1: (4-bromo-3-fluoro-phenyl)-carbamic acid methyl ester With lithium tert-butoxide In methanol; N,N-dimethyl-formamide at 5℃; for 1.5h; Inert atmosphere; Stage #2: N-[(2S)-2-acetoxy-3-chloropropyl]acetamide In methanol; N,N-dimethyl-formamide at 25℃; for 20h; Inert atmosphere;	82.5%
With lithium tert-butoxide In methanol; N,N-dimethyl-formamide at 20℃; for 20h;

[4-(3,6-dihydro-2H-pyridin-1-yl)-3-fluoro-phenyl]-carbamic acid benzyl ester (847256-99-9) + N-[(2S)-2-acetoxy-3-chloropropyl]acetamide (183905-31-9) → N-{3-[4-(3,6-dihydro-2H-pyridin-1-yl)-3-fluoro-phenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide (847257-00-5)

Conditions	Yield
Stage #1: [4-(3,6-dihydro-2H-pyridin-1-yl)-3-fluoro-phenyl]-carbamic acid benzyl ester With lithium tert-butoxide In tetrahydrofuran; methanol; DMF (N,N-dimethyl-formamide) at 0 - 20℃; Stage #2: N-[(2S)-2-acetoxy-3-chloropropyl]acetamide In tetrahydrofuran; methanol; DMF (N,N-dimethyl-formamide) at 0 - 20℃;	82%

N-benzyloxycarbonyl-3-fluoro-4-(4-(pyridin-2-yl)-1H-pyrazol-1-yl)aniline (1416314-75-4) + N-[(2S)-2-acetoxy-3-chloropropyl]acetamide (183905-31-9) → (S)-N-((3-(3-fluoro-4-(4-(pyridin-2-yl)-1H-pyrazol-1-yl)-phenyl)-2-oxooxazolidin-5-yl)methyl)acetamide (1416314-55-0)

Conditions	Yield
Stage #1: N-benzyloxycarbonyl-3-fluoro-4-(4-(pyridin-2-yl)-1H-pyrazol-1-yl)aniline; N-[(2S)-2-acetoxy-3-chloropropyl]acetamide With methanol In tetrahydrofuran at -5℃; for 0.166667h; Inert atmosphere; Stage #2: With lithium tert-butoxide In tetrahydrofuran at -5 - 17℃; for 16h; Inert atmosphere; Stage #3: With acetic acid In tetrahydrofuran at 10℃; for 0.5h; Inert atmosphere;	82%
With lithium tert-butoxide In tetrahydrofuran; methanol at -5 - 20℃; Concentration; Inert atmosphere; Large scale;	82%
Stage #1: N-benzyloxycarbonyl-3-fluoro-4-(4-(pyridin-2-yl)-1H-pyrazol-1-yl)aniline With lithium tert-butoxide In tetrahydrofuran for 0.0833333h; Inert atmosphere; Cooling with ice; Stage #2: N-[(2S)-2-acetoxy-3-chloropropyl]acetamide In tetrahydrofuran at 20℃; for 36h; Cooling with ice;	38.2%
Stage #1: N-benzyloxycarbonyl-3-fluoro-4-(4-(pyridin-2-yl)-1H-pyrazol-1-yl)aniline With lithium tert-butoxide In tetrahydrofuran for 0.0833333h; Inert atmosphere; Cooling with ice; Stage #2: N-[(2S)-2-acetoxy-3-chloropropyl]acetamide In tetrahydrofuran at 20℃; for 36h;	38.2%

benzyl 3-fluoro-4-(4-morpholinyl)phenylcarbamate (168828-81-7, 1027135-00-7) + N-[(2S)-2-acetoxy-3-chloropropyl]acetamide (183905-31-9) → linezolid (165800-03-3)

Conditions	Yield
Stage #1: benzyl 3-fluoro-4-(4-morpholinyl)phenylcarbamate With lithium tert-butoxide In tetrahydrofuran; methanol; N,N-dimethyl-formamide Stage #2: N-[(2S)-2-acetoxy-3-chloropropyl]acetamide at 21℃; for 21h; Solvent;	80.6%
Stage #1: benzyl 3-fluoro-4-(4-morpholinyl)phenylcarbamate With lithium tert-butoxide In tetrahydrofuran; methanol at 10 - 25℃; Large scale; Stage #2: N-[(2S)-2-acetoxy-3-chloropropyl]acetamide at 8℃; Temperature; Large scale;
With lithium tert-butoxide In tetrahydrofuran; methanol at 20℃; for 16h;	83 g
Stage #1: benzyl 3-fluoro-4-(4-morpholinyl)phenylcarbamate With lithium tert-butoxide In tetrahydrofuran; methanol; N,N-dimethyl-formamide at 0 - 5℃; for 4h; Inert atmosphere; Stage #2: N-[(2S)-2-acetoxy-3-chloropropyl]acetamide In tetrahydrofuran; methanol; N,N-dimethyl-formamide at 0 - 20℃; for 46h; Temperature; Inert atmosphere;

isobutyl 4-(1,1-dioxidothiomorpholin-4-yl)-3,5-difluorophenylcarbamate (473871-38-4) + N-[(2S)-2-acetoxy-3-chloropropyl]acetamide (183905-31-9) → PNU-288034

Conditions	Yield
Stage #1: isobutyl 4-(1,1-dioxidothiomorpholin-4-yl)-3,5-difluorophenylcarbamate; N-[(2S)-2-acetoxy-3-chloropropyl]acetamide With methanol In acetonitrile at 0 - 5℃; Large scale; Stage #2: With lithium tert-butoxide In tetrahydrofuran; acetonitrile at 16℃; Temperature; Time; Solvent; Large scale;	80.3%
With lithium tert-butoxide In tetrahydrofuran; methanol; acetonitrile at 4 - 16℃; for 15.5h; Solvent; Time; Temperature;	77.6%

(3-fluoro-4-iodophenyl)carbamic acid methyl ester + N-[(2S)-2-acetoxy-3-chloropropyl]acetamide (183905-31-9) → (S)-N-[3-(3-fluoro-4-iodophenyl)-2-oxo-1,3-oxazolidine-5-ylmethyl]acetamide (149524-45-8)

Conditions	Yield
Stage #1: (3-fluoro-4-iodophenyl)carbamic acid methyl ester With lithium tert-butoxide In methanol; N,N-dimethyl-formamide at 45℃; for 1.5h; Inert atmosphere; Stage #2: N-[(2S)-2-acetoxy-3-chloropropyl]acetamide In methanol; N,N-dimethyl-formamide at 20℃; for 30h; Inert atmosphere;	79.5%
Stage #1: (3-fluoro-4-iodophenyl)carbamic acid methyl ester With lithium tert-butoxide In N,N-dimethyl-formamide at 30 - 35℃; for 1h; Inert atmosphere; Stage #2: With methanol In N,N-dimethyl-formamide at 5 - 10℃; for 1.5h; Inert atmosphere; Stage #3: N-[(2S)-2-acetoxy-3-chloropropyl]acetamide In N,N-dimethyl-formamide at 20℃; for 24h; Inert atmosphere;	79.5%
Stage #1: (3-fluoro-4-iodophenyl)carbamic acid methyl ester With lithium tert-butoxide In N,N-dimethyl-formamide at 30 - 35℃; for 1h; Inert atmosphere; Stage #2: With methanol In N,N-dimethyl-formamide at 5 - 10℃; for 1.5h; Inert atmosphere; Stage #3: N-[(2S)-2-acetoxy-3-chloropropyl]acetamide In N,N-dimethyl-formamide at 10 - 20℃; for 24h; Inert atmosphere;	79.5%
In methanol at 25℃; for 24h;

methyl N-(3-iodo-4-fluorophenyl)carbamate + N-[(2S)-2-acetoxy-3-chloropropyl]acetamide (183905-31-9) → (S)-N-[3-(3-fluoro-4-iodophenyl)-2-oxo-1,3-oxazolidine-5-ylmethyl]acetamide (149524-45-8)

Conditions	Yield
Stage #1: methyl N-(3-iodo-4-fluorophenyl)carbamate With methanol; potassium tert-butylate In N,N-dimethyl-formamide at 0 - 5℃; for 1.5h; Inert atmosphere; Stage #2: N-[(2S)-2-acetoxy-3-chloropropyl]acetamide In N,N-dimethyl-formamide at 25℃; for 24h; Inert atmosphere;	79.5%

N-[(2S)-2-acetoxy-3-chloropropyl]acetamide (183905-31-9) + benzyl benzyl(4-(((benzyloxy)carbonyl)amino)-2-fluorophenyl)carbamate (181997-29-5) → benzyl 4-{(5S)-5-[(acetylamino)methyl]-2-oxo-1,3-oxazolidin-3-yl}-2-fluorophenyl(benzyl)carbamate (182059-57-0)

Conditions	Yield
Stage #1: benzyl benzyl(4-{[(benzyloxy)carbonyl]amino}-2-fluorophenyl)carbamate With lithium tert-butoxide In tetrahydrofuran at -5℃; for 0.25h; Inert atmosphere; Stage #2: N-[(2S)-2-acetoxy-3-chloropropyl]acetamide With acetic acid In tetrahydrofuran; methanol at 0 - 5℃; for 17h;	79%
Stage #1: benzyl benzyl(4-{[(benzyloxy)carbonyl]amino}-2-fluorophenyl)carbamate With lithium tert-butoxide In tetrahydrofuran for 0.25h; Inert atmosphere; Cooling with ice; Stage #2: N-[(2S)-2-acetoxy-3-chloropropyl]acetamide In tetrahydrofuran at 20℃;	51.1%
Stage #1: benzyl benzyl(4-{[(benzyloxy)carbonyl]amino}-2-fluorophenyl)carbamate With lithium tert-butoxide In tetrahydrofuran for 0.25h; Inert atmosphere; Cooling with ice; Stage #2: N-[(2S)-2-acetoxy-3-chloropropyl]acetamide In tetrahydrofuran; methanol at 20℃;	51.1%

(3-fluoro-4-iodophenyl)carbamic acid benzyl ester (1097722-53-6) + N-[(2S)-2-acetoxy-3-chloropropyl]acetamide (183905-31-9) → (S)-N-[3-(3-fluoro-4-iodophenyl)-2-oxo-1,3-oxazolidine-5-ylmethyl]acetamide (149524-45-8)

Conditions	Yield
Stage #1: (3-fluoro-4-iodophenyl)carbamic acid benzyl ester With lithium tert-butoxide In methanol; N,N-dimethyl-formamide at 45℃; for 1.5h; Inert atmosphere; Stage #2: N-[(2S)-2-acetoxy-3-chloropropyl]acetamide In methanol; N,N-dimethyl-formamide at 20℃; for 30h; Inert atmosphere;	78.5%

[3,5-difluoro-4-(4-hydroxy-4-methoxymethyl-piperidin-1-yl)-phenyl]-carbamic acid benzyl ester (1207472-10-3) + N-[(2S)-2-acetoxy-3-chloropropyl]acetamide (183905-31-9) → (5S)-N-{3-[3,5-difluoro-4-(4-hydroxy-4-methoxymethyl-piperidin-1-yl)phenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide (957796-51-9)

Conditions	Yield
Stage #1: [3,5-difluoro-4-(4-hydroxy-4-methoxymethyl-piperidin-1-yl)-phenyl]-carbamic acid benzyl ester With lithium 2-methylpropan-2-olate In tetrahydrofuran at 20℃; for 3h; Stage #2: N-[(2S)-2-acetoxy-3-chloropropyl]acetamide In tetrahydrofuran; methanol at 10 - 20℃; for 21h;	77%

N-[(2S)-2-acetoxy-3-chloropropyl]acetamide (183905-31-9) + 2-methylpropyl [3-fluoro-4-(tetrahydro-2H-thiopyran-4-yl)phenyl]carbamate (288570-78-5) → N-{[(5S)-3-(3-fluoro-4-tetrahydro-2H-thiopyran-4-ylphenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide

Conditions	Yield
With 2-methylbutan-2-ol (lithium salt) In methanol; N,N-dimethyl-formamide at 2 - 23℃;	73.9%

{4-[(1α,5α,6α)-6-(tert-butyldimethylsilanyloxy)-3-azabicyclo[3.1.0]hex-3-yl]-3,5-difluorophenyl}carbamic acid benzyl ester (681425-46-7) + N-[(2S)-2-acetoxy-3-chloropropyl]acetamide (183905-31-9) → (S)-N-(3-{4-[(1α,5α,6α)-6-(tert-butyldimethylsilanyloxy)-3-azabicyclo[3.1.0]hex-3-yl]-3,5-difluorophenyl}-2-oxooxazolidin-5-ylmethyl)acetamide

Conditions	Yield
With lithium tert-butoxide In tetrahydrofuran; methanol; N,N-dimethyl-formamide at 20℃; for 20h;	73%
With methanol; lithium butoxide In tetrahydrofuran; DMF (N,N-dimethyl-formamide) at 0 - 20℃; for 20h;	73%

(1α,5α,6α)-3-(4-benzyloxycarbonylamino-2,6-difluorophenyl)-3-azabicyclo[3.1.0]hexane-6-carboxylic acid tert-butyl ester (681424-90-8) + N-[(2S)-2-acetoxy-3-chloropropyl]acetamide (183905-31-9) → (S)-(1α,5α,6α)-3-{4-[5-(acetylaminomethyl)-2-oxooxazolidin-3-yl]-2,6-difluorophenyl}-3-azabicyclo[3.1.0]hexane-6-carboxylic acid tert-butyl ester (681424-86-2)

Conditions	Yield
With lithium tert-butoxide In tetrahydrofuran; methanol; N,N-dimethyl-formamide at 20℃; for 20h;	72%
With methanol; lithium butoxide In tetrahydrofuran; DMF (N,N-dimethyl-formamide) at 0 - 20℃; for 20h;	72%

[9-(tetrahydro-pyran-2-yloxy)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-3-yl]-carbamic acid ethyl ester (741721-64-2) + N-[(2S)-2-acetoxy-3-chloropropyl]acetamide (183905-31-9) → N-{2-oxo-3-[9-(tetrahydro-pyran-2-yloxy)-6,7.8.9-tetrahydro-5H-cyclohepta[b]pyridin-3-yl]-oxazolidin-5(S)-ylmethyl}-acetamide (741721-66-4)

Conditions	Yield
With lithium tert-butoxide In methanol; N,N-dimethyl-formamide	71%
Stage #1: [9-(tetrahydro-pyran-2-yloxy)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-3-yl]-carbamic acid ethyl ester With methanol; lithium tert-butoxide In DMF (N,N-dimethyl-formamide); hexane at 20℃; for 1h; Stage #2: N-[(2S)-2-acetoxy-3-chloropropyl]acetamide In DMF (N,N-dimethyl-formamide); hexane at 0 - 20℃;

isopropyl 3,5-difluoro-4-[exo-(1R,5S)-3-oxabicyclo[3.1.0]hex-6-yl]phenylcarbamate + N-[(2S)-2-acetoxy-3-chloropropyl]acetamide (183905-31-9) → N-[((5S)-3-{3,5-difluoro-4-[exo-(1R,5S)-3-oxabicyclo[3.1.0]hex-6-yl]phenyl}-2-oxo-1,3-oxazolidin-5-yl)methyl]acetamide

Conditions	Yield
With lithium tert-butoxide In methanol; DMF (N,N-dimethyl-formamide) at 0 - 20℃; for 20h;	71%

[4-(3-azabicyclo[3.1.0]hex-3-yl)-3,5-difluorophenyl]carbamic acid benzyl ester (681425-48-9) + N-[(2S)-2-acetoxy-3-chloropropyl]acetamide (183905-31-9) → (S)-N-{3-[4-(3-azabicyclo[3.1.0]hex-3-yl)-3,5-difluorophenyl]-2-oxooxazolidin-5-ylmethyl}acetamide

Conditions	Yield
With lithium tert-butoxide In tetrahydrofuran; methanol; N,N-dimethyl-formamide at 20℃; for 20h;	70%
With methanol; lithium butoxide In tetrahydrofuran; DMF (N,N-dimethyl-formamide) at 0 - 20℃; for 20h;	70%

[(1α,5α,6α)-3-(4-benzyloxycarbonylamino-2,6-difluorophenyl)-3-azabicyclo[3.1.0]hex-6-yl]carbamic acid tert-butyl ester (681425-28-5) + N-[(2S)-2-acetoxy-3-chloropropyl]acetamide (183905-31-9) → (S)-((1α,5α,6α)-3-{4-[5-(acetylaminomethyl)-2-oxooxazolidin-3-yl]-2,6-difluorophenyl}-3-azabicyclo[3.1.0]hex-6-yl)carbamic acid tert-butyl ester (681425-26-3)

Conditions	Yield
With lithium tert-butoxide In tetrahydrofuran; methanol; N,N-dimethyl-formamide at 20℃; for 20h;	70%
With methanol; lithium butoxide In tetrahydrofuran; DMF (N,N-dimethyl-formamide) at 0 - 20℃; for 20h;	70%

benzyl 3-fluoro-4-[exo-(1R,5S)-3-oxabicyclo[3.1.0]hex-6-yl]phenylcarbamate + N-[(2S)-2-acetoxy-3-chloropropyl]acetamide (183905-31-9) → N-[((5S)-3-{3-fluoro-4-[exo-(1R,5S)-3-oxabicyclo[3.1.0]hex-6-yl]phenyl}-2-oxo-1,3-oxazolidin-5-yl)methyl]acetamide

Conditions	Yield
With lithium tert-butoxide In methanol; DMF (N,N-dimethyl-formamide) at 0 - 20℃; for 20h;	70%

benzyl 3-fluoro-4-[(1α,5α,6β)-3-thiabicyclo[3.1.0]hex-6-yl]phenylcarbamate (858367-38-1) + N-[(2S)-2-acetoxy-3-chloropropyl]acetamide (183905-31-9) → N-[((5S)-3-{3-fluoro-4-[(1α,5α,6β)-3-thiabicyclo[3.1.0]hex-6-yl]phenyl}-2-oxo-1,3-oxazolidin-5-yl)methyl]acetamide

Conditions	Yield
With lithium tert-butoxide In tetrahydrofuran; methanol; N,N-dimethyl-formamide at 0 - 20℃; for 20h;	68%
With methanol; lithium tert-butoxide In N,N-dimethyl-formamide

Upstream product

• 108-24-7 acetic anhydride 
• 34839-13-9 (2S)-1-amino-3-chloropropan-2-ol hydrogen chloride 
• 75-05-8 acetonitrile 
• 34839-13-9 (S)-1-amino-3-chloro-2-propanol hydrochloride 
• 75-36-5 acetyl chloride 
• 53494-57-8 (S)-1-amino-3-chloropropan-2-ol 

Downstream Products

• 777089-65-3 N-[((5S)-3-{4-[(1α,5α,6β)-3-(4-methoxybenzyl)-3-azabicyclo[3.1.0]hex-6-yl]phenyl}-2-oxo-1,3-oxazolidin-5-yl)methyl]acetamide 
• 777089-36-8 N-[((5S)-3-{3-fluoro-4-[exo-(1α,5α,6β)-3-(4-methoxybenzyl)-3-azabicyclo[3.1.0]hex-6-yl]phenyl}-2-oxo-1,3-oxazolidin-5-yl)methyl]acetamide 
• 681424-86-2 (S)-(1α,5α,6α)-3-{4-[5-(acetylaminomethyl)-2-oxooxazolidin-3-yl]-2,6-difluorophenyl}-3-azabicyclo[3.1.0]hexane-6-carboxylic acid tert-butyl ester 
• 881012-72-2 N-((S)-3-{3,5-Difluoro-4-[(1S,5R,6S)-3-(4-methoxy-benzyl)-3-aza-bicyclo[3.1.0]hex-6-yl]-phenyl}-2-oxo-oxazolidin-5-ylmethyl)-acetamide 
• 681425-26-3 (S)-((1α,5α,6α)-3-{4-[5-(acetylaminomethyl)-2-oxooxazolidin-3-yl]-2,6-difluorophenyl}-3-azabicyclo[3.1.0]hex-6-yl)carbamic acid tert-butyl ester 
• 847257-41-4 N-(3-{4-[6-(tert-butyl-dimethyl-silanyloxy)-1,4-dioxa-spiro[4.5]dec-8-yl]-3-fluoro-phenyl}-2-oxo-oxazolidin-5-ylmethyl)-acetamide 
• 919357-43-0 N-({(5S)-3-[3-fluoro-4-(3-{tert-butyldimethylsilyloxy}-cyclobutyl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide 
• 919357-44-1 N-({(5S)-3-[3,5-difluoro-4-(3-{tert-butyldimethylsilyloxy}-cyclobutyl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide 
• 919350-20-2 N-(((S)-3-(3-fluoro-4-((l1R,3S)-3-hydroxycyclobutyl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamide 

Relevant articles and documents

Diol-Ritter Reaction: Regio- And Stereoselective Synthesis of Protected Vicinal Aminoalcohols and Mechanistic Aspects of Diol Monoester Disproportionation

The well-known epoxide-Ritter reaction generally affords oxazolines with poor to average regioselectivity. Herein, a mechanism-based study of the less known diol-Ritter reaction has provided a highly regioselective procedure for the synthesis of 1-vic-amido-2-esters from either terminal epoxides or 1,2-diols via Lewis acid-catalyzed monoesterification. When treated with a stoichiometric Lewis acid catalyst (BF3), these diol monoesters form dioxonium cation intermediates that are ring-opened with nitrile nucleophiles to form nitrilium intermediates, which undergo rapid and irreversible hydration to give the desired amidoesters. Diester byproduct formation is irreversible and appears to occur through disproportionation of diol monoester. With chiral epoxide starting materials, the formation of amidoester occurs with retention of configuration and no apparent erosion of optical purity as determined by single-crystal X-ray analyses and chiral chromatography, respectively. The direct access to chiral vic-amidoesters is especially practical with regard to the synthesis of antibacterial oxazolidinone analogues of the Zyvox antimicrobial family.

OXAZOLIDINONE COMPOUNDS AND METHODS OF USE THEREOF AS ANTIBACTERIAL AGENTS

The present invention relates to oxazolidinone compounds of Formula (I): and pharmaceutically acceptable salts thereof, wherein A, E, and R1 are as defined herein. The present invention also relates to compositions which comprise at least one oxazolidinone compound of the invention. The invention also provides methods for inhibiting growth of mycobacterial cells as well as a method of treating mycobacterial infections by Mycobacterium tuberculosiscomprising administering a therapeutically effective amount of an oxazolidinone of the invention and/or apharmaceutically acceptable salt thereof, or a composition comprising such compound and/or salt.

PROCESS FOR THE PREPARATION OF (5S)-N-{3-[3,5-DIFLUORO-4-(4-HYDROXY-4-METHOXYMETHYL-PIPERIDIN-1-YL)-PHENYL]-2-OXO-OXAZOLIDIN-5-YLMETHYL}-ACETAMIDE

A process for preparation of compound of Formula (I) is provided.