168828-82-8

Basic information

• Product Name: (5R)-3-(3-Fluoro-4-(4-morpholinyl)phenyl)-5-hydroxymethyl-2-oxazolidione
• Synonyms: (R)-3-(3-FLUORO-4-MORPHOLINOPHENYL)-5-(HYDROXYMETHYL)OXAZOLIDIN-2-ONE;R-N-(3-FLUORO-4-MORPHOLINYLPHENYL)-2-OXO-5-OXAZOLIDINYLMETHANOL;(5R)-3-[3-FLUORO-4-(4-MORPHOLINYL)PHENYL]-5-(HYDROXYMETHYL)-2-OXAZOLIDINONE;2-Oxazolidinone, 3-[3-fluoro-4-(4-morpholinyl)phenyl]-5-(hydroxymethyl)-, (5R)-;3-(3-FLUORO-4-(4-MORPHOLINYL)PHENYL)-5-HYDROXYMETHYL-(5R)-2-OXAZOLIDIONE;2-Oxazolidinone,3-[3-fluoro-4-(4-morpholinyl)phen;R)-5-(Hydroxymethyl)-3-(3-fluoro-4-morpholinopheny;(5R)-3-[3-Fluoro-4-(4-morpholinyl)phenyl]-5-(hydroxymethyl)-2-oxazolindinone
• CAS NO: 168828-82-8
• Molecular Formula: C₁₄H₁₇FN₂O₄
• Molecular Weight: 296.3
• EINECS: 1806241-263-5
• Mol File: 168828-82-8.mol
• Article Data: 26

Chemical Properties

• Melting Point: 110-112 °C
• Boiling Point: 494.241 °C at 760 mmHg
• Flash Point: 252.708 °C
• Appearance: /
• Density: 1.362 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.572
• Storage Temp.: 2-8°C
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: 14.05±0.10(Predicted)
• CAS DataBase Reference: (5R)-3-(3-Fluoro-4-(4-morpholinyl)phenyl)-5-hydroxymethyl-2-oxazolidione(CAS DataBase Reference)
• NIST Chemistry Reference: (5R)-3-(3-Fluoro-4-(4-morpholinyl)phenyl)-5-hydroxymethyl-2-oxazolidione(168828-82-8)
• EPA Substance Registry System: (5R)-3-(3-Fluoro-4-(4-morpholinyl)phenyl)-5-hydroxymethyl-2-oxazolidione(168828-82-8)

Safety Data

• Hazardous Substances Data: 168828-82-8(Hazardous Substances Data)

Usage

Uses

[(R)-3-(3-Fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl]methanol is an intermediate in the synthesis of Linezolid Dimer (L466520), an impurity of the antibacterial agent Linezolid (L466500).

InChI:InChI=1/C14H17FN2O4/c15-12-7-10(17-8-11(9-18)21-14(17)19)1-2-13(12)16-3-5-20-6-4-16/h1-2,7,11,18H,3-6,8-9H2/t11-/m1/s1

Synthetic route

((S)-2,3-Dihydroxy-propyl)-(3-fluoro-4-morpholin-4-yl-phenyl)-carbamic acid benzyl ester (912552-56-8) → (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol (168828-82-8)

Conditions	Yield
With sodium hydride In tetrahydrofuran at 0℃;	96%

(R)-glycidyl butyrate (60456-26-0) + benzyl 3-fluoro-4-(4-morpholinyl)phenylcarbamate (168828-81-7, 1027135-00-7) → (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol (168828-82-8)

Conditions	Yield
Stage #1: benzyl 3-fluoro-4-(4-morpholinyl)phenylcarbamate With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1h; Inert atmosphere; Stage #2: (R)-glycidyl butyrate In tetrahydrofuran; hexane at -78 - 20℃; Stage #3: With ammonium chloride In tetrahydrofuran; hexane; water	85.1%
Stage #1: benzyl 3-fluoro-4-(4-morpholinyl)phenylcarbamate With n-butyllithium; butan-1-ol In tetrahydrofuran; hexane at -15 - 30℃; Inert atmosphere; Stage #2: (R)-glycidyl butyrate In tetrahydrofuran; hexane at -10 - 15℃; Stage #3: With water In tetrahydrofuran; hexane; ethyl acetate	85%
Stage #1: benzyl 3-fluoro-4-(4-morpholinyl)phenylcarbamate With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1.63333h; Stage #2: (R)-glycidyl butyrate In tetrahydrofuran; hexane at -78 - 20℃; for 22.1h;	83%

carbon dioxide (124-38-9) + (S)-N-(2,3-epoxy-1-propyl)-3-fluoro-4-(4-morpholinyl)aniline → (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol (168828-82-8)

Conditions	Yield
With dmap; C20H14AlNO3 In dichloromethane at 25℃; under 760.051 Torr; for 60h; Sealed tube; stereoselective reaction;	85%

N-ethoxycarbonyl-3-fluoro-4-morpholinyl aniline (565176-83-2) + (R)-glycidyl butyrate (60456-26-0) → (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol (168828-82-8)

Conditions	Yield
Stage #1: N-ethoxycarbonyl-3-fluoro-4-morpholinyl aniline With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 3.5h; Inert atmosphere; Stage #2: (R)-glycidyl butyrate In tetrahydrofuran; hexane at -78 - 20℃; Stage #3: With ammonium chloride In tetrahydrofuran; hexane; water at 20℃; for 0.5h; Product distribution / selectivity;	80%

N-[4(R)-(2,2-dimethyl-1,3-dioxolane-4-yl)methyl]-3-fluoro-4-morpholinylaniline (903593-93-1) + bis(trichloromethyl) carbonate (32315-10-9) → (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol (168828-82-8)

Conditions	Yield
Stage #1: N-[4(R)-(2,2-dimethyl-1,3-dioxolane-4-yl)methyl]-3-fluoro-4-morpholinylaniline With hydrogenchloride; water In methanol at 20℃; for 8h; Stage #2: bis(trichloromethyl) carbonate With sodium carbonate at 20℃; for 24h; Further stages.;	56%

(5R)-3-[3-fluoro-4-(4-morpholinyl)phenyl]-5-carbaldehyde-2-oxazolidinone → (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol (168828-82-8)

Conditions	Yield
With sodium tetrahydroborate In methanol at 0℃; Yield given;

(R)-glycidyl butyrate (60456-26-0) + 3-fluoro-4-(morpholinyl)aniline (93246-53-8) → (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol (168828-82-8)

Conditions	Yield
Multistep reaction;

3-(3-fluoro-4-morpholin-4-yl-phenylamino)-propan-1-ol → (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol (168828-82-8)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: aq. NaHCO3 / acetone 2.1: 95 percent / (COCl)2; DMSO; Et3N / CH2Cl2 / -78 - -60 °C 3.1: nitrosobenzene; D-proline / acetonitrile / 24 h / -20 °C 3.2: NaBH4 / methanol 3.3: 86 percent / CuSO4 / methanol 4.1: 96 percent / sodium hydride / tetrahydrofuran / 0 °C View Scheme

(3-fluoro-4-morpholin-4-yl-phenyl)-(3-oxo-propyl)-carbamic acid benzyl ester (912552-55-7) → (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol (168828-82-8)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: nitrosobenzene; D-proline / acetonitrile / 24 h / -20 °C 1.2: NaBH4 / methanol 1.3: 86 percent / CuSO4 / methanol 2.1: 96 percent / sodium hydride / tetrahydrofuran / 0 °C View Scheme

(3-fluoro-4-morpholin-4-yl-phenyl)-(3-hydroxy-propyl)-carbamic acid benzyl ester (912552-54-6) → (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol (168828-82-8)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: 95 percent / (COCl)2; DMSO; Et3N / CH2Cl2 / -78 - -60 °C 2.1: nitrosobenzene; D-proline / acetonitrile / 24 h / -20 °C 2.2: NaBH4 / methanol 2.3: 86 percent / CuSO4 / methanol 3.1: 96 percent / sodium hydride / tetrahydrofuran / 0 °C View Scheme

3-fluoro-4-(morpholinyl)aniline (93246-53-8) → (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol (168828-82-8)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: NaI; Na2CO3 / dimethylformamide / 65 °C 2.1: aq. NaHCO3 / acetone 3.1: 95 percent / (COCl)2; DMSO; Et3N / CH2Cl2 / -78 - -60 °C 4.1: nitrosobenzene; D-proline / acetonitrile / 24 h / -20 °C 4.2: NaBH4 / methanol 4.3: 86 percent / CuSO4 / methanol 5.1: 96 percent / sodium hydride / tetrahydrofuran / 0 °C View Scheme
Multi-step reaction with 2 steps 1.1: NaHCO3 2.1: n-BuLi / tetrahydrofuran; hexane / -78 °C 2.2: hexane; tetrahydrofuran / -78 - 20 °C View Scheme
Multi-step reaction with 2 steps 1: 70 percent / sodium bicarbonate / acetone; H2O 2: 1.) n-butyllithium / 1.) THF, hexane, -78 deg C, 35 min, 2.) THF, hexane, -78 deg C, 1 h View Scheme

3,4-difluoronitrobenzene (369-34-6) → (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol (168828-82-8)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: N,N-diisopropylethylamine 2.1: ammonium formate / 10 percent Pd/C / methanol; tetrahydrofuran 3.1: NaHCO3 4.1: n-BuLi / tetrahydrofuran; hexane / -78 °C 4.2: hexane; tetrahydrofuran / -78 - 20 °C View Scheme
Multi-step reaction with 3 steps 1: N,N-diisopropylethylamine / acetonitrile / 17 h / Heating 2: H2 / PtO2 / methanol / 3 h / 20 °C / 1471.02 Torr View Scheme
Multi-step reaction with 4 steps 1: 98 percent / N,N-diisopropylethylamine / ethyl acetate 2: ammonium formate / 10percent Pd/C 3: 70 percent / sodium bicarbonate / acetone; H2O 4: 1.) n-butyllithium / 1.) THF, hexane, -78 deg C, 35 min, 2.) THF, hexane, -78 deg C, 1 h View Scheme

3-fluoro-4-(4-morpholinyl)nitrobenzene (2689-39-6) → (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol (168828-82-8)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: ammonium formate / 10 percent Pd/C / methanol; tetrahydrofuran 2.1: NaHCO3 3.1: n-BuLi / tetrahydrofuran; hexane / -78 °C 3.2: hexane; tetrahydrofuran / -78 - 20 °C View Scheme
Multi-step reaction with 2 steps 1: H2 / PtO2 / methanol / 3 h / 20 °C / 1471.02 Torr View Scheme
Multi-step reaction with 3 steps 1: ammonium formate / 10percent Pd/C 2: 70 percent / sodium bicarbonate / acetone; H2O 3: 1.) n-butyllithium / 1.) THF, hexane, -78 deg C, 35 min, 2.) THF, hexane, -78 deg C, 1 h View Scheme

(R)-2-(3-Fluoro-4-morpholin-4-yl-phenylamino)-1-{(4R,5R)-5-[(R)-2-(3-fluoro-4-morpholin-4-yl-phenylamino)-1-hydroxy-ethyl]-2,2-dimethyl-[1,3]dioxolan-4-yl}-ethanol (905945-96-2) → (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol (168828-82-8)

Conditions	Yield
Multi-step reaction with 4 steps 1: CH2Cl2 / Ambient temperature 2: 2N HCl / Ambient temperature 3: lead tetraacetate (LTA) / tetrahydrofuran / 0 °C 4: NaBH4 / methanol / 0 °C View Scheme

C28H32F2N4O8 (239438-43-8) → (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol (168828-82-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: lead tetraacetate (LTA) / tetrahydrofuran / 0 °C 2: NaBH4 / methanol / 0 °C View Scheme

C31H36F2N4O8 (239438-39-2) → (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol (168828-82-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: 2N HCl / Ambient temperature 2: lead tetraacetate (LTA) / tetrahydrofuran / 0 °C 3: NaBH4 / methanol / 0 °C View Scheme

N-[3-chloro-2-(R)-hydroxypropyl]-3-fluoro-4-(morpholin-4-yl)aniline (868405-66-7) → (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol (168828-82-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1,1'-carbonyldiimidazole / dichloromethane / 24 h / 20 - 30 °C 2: N,N-dimethyl-formamide / 120 °C 3: water; sodium t-butanolate / tetrahydrofuran / 0.5 h / 0 - 15 °C View Scheme
Multi-step reaction with 3 steps 1: dichloromethane / 24 h / 25 - 30 °C 2: N,N-dimethyl-formamide / 120 °C 3: sodium t-butanolate; water / tetrahydrofuran / 0.5 h / 0 - 15 °C View Scheme

(5R)-5-(chloromethyl)-3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxazolidinone → (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol (168828-82-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: N,N-dimethyl-formamide / 120 °C 2: water; sodium t-butanolate / tetrahydrofuran / 0.5 h / 0 - 15 °C View Scheme
Multi-step reaction with 2 steps 1: N,N-dimethyl-formamide / 120 °C 2: sodium t-butanolate; water / tetrahydrofuran / 0.5 h / 0 - 15 °C View Scheme

(R)-(3-(3-fluoro-4-morpholinophenyl)-2-oxooxazolidin-5-yl)methyl acetate (496031-56-2) → (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol (168828-82-8)

Conditions	Yield
With water; sodium t-butanolate In tetrahydrofuran at 0 - 15℃; for 0.5h;
With water; sodium t-butanolate In tetrahydrofuran at 0 - 15℃; for 0.5h;	50 g

(S)-3-chloropropan-1,2-diol (60827-45-4) + benzyl 3-fluoro-4-(4-morpholinyl)phenylcarbamate (168828-81-7, 1027135-00-7) → (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol (168828-82-8)

Conditions	Yield
With potassium tert-butylate; lithium diisopropyl amide

(2R)-1-chloro-3-{[3-fluoro-4-(morpholin-4-yl)phenyl]amino}-propan-2-ol → (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol (168828-82-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydroxide / dichloromethane; water / 24 h 2: dmap; C20H14AlNO3 / dichloromethane / 60 h / 25 °C / 760.05 Torr / Sealed tube View Scheme

methanesulfonyl chloride (124-63-0) + (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol (168828-82-8) → (R)-methyl methanesulfonate (174649-09-3)

Conditions	Yield
With triethylamine In dichloromethane at 0℃; for 0.5h;	100%
With triethylamine In tetrahydrofuran at 8 - 15℃; for 3.75h; Cooling with ice; Inert atmosphere;	96%
With triethylamine In dichloromethane at 20 - 30℃;	95%

p-toluenesulfonyl chloride (98-59-9) + (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol (168828-82-8) → (R)-[N-3-(3-fluoro-4-morpholinylphenyl)-2-oxo-5-oxazolidinyl]methyl 4-methylbenzenesulfonate (168828-83-9)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃;	92%
With triethylamine In dichloromethane at 0 - 20℃; for 18.8333h;	92%
With triethylamine In dichloromethane at 0 - 20℃; for 18h;	85%

4-iodobenzenesulfonyl chloride (98-61-3) + (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol (168828-82-8) → (R)-[3-(3-fluoro-4-morpholin-4-ylphenyl)-2-oxo-5-oxazolidinyl]methyl p-iodobenzenesulfonate

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 18h;	82.5%

4-bromobenzenesulfonyl chloride (98-58-8) + (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol (168828-82-8) → (R)-[3-(3-fluoro-4-morpholin-4-ylphenyl)-2-oxo-5-oxazolidinyl]methyl p-bromobenzenesulfonate

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 26h;	81.5%

(R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol (168828-82-8) + thioacetic acid (507-09-5) → linezolid (165800-03-3)

Conditions	Yield
Stage #1: (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol With methanesulfonyl chloride Stage #2: With sodium azide Stage #3: tiolacetic acid stereoselective reaction;	81%

4-Fluorobenzenesulfonyl chloride (349-88-2) + (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol (168828-82-8) → (R)-[3-(3-fluoro-4-morpholin-4-ylphenyl)-2-oxo-5-oxazolidinyl]methyl p-fluorobenzenesulfonate

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 18h;	80.3%

(R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol (168828-82-8) → (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0)

Conditions	Yield
Stage #1: (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol With methanesulfonyl chloride; triethylamine In dichloromethane at 0 - 20℃; Stage #2: With sodium azide In N,N-dimethyl-formamide at 80℃; Further stages.;	79%
Multi-step reaction with 2 steps 1: Et3N / CH2Cl2 / 4 h / 0 °C 2: NaN3 / dimethylformamide / 75 °C View Scheme
Multi-step reaction with 2 steps 1: Et3N / tetrahydrofuran / 2 h / 20 °C 2: sodium azide / dimethylformamide / 6 h / 65 °C View Scheme

acetic anhydride (108-24-7) + (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol (168828-82-8) → (R)-(3-(3-fluoro-4-morpholinophenyl)-2-oxooxazolidin-5-yl)methyl acetate (496031-56-2)

Conditions	Yield
With pyridine; dmap In dichloromethane at 20℃; for 4h;	75%

isoxazol-3-ol (5777-20-8) + diisopropyl (E)-azodicarboxylate (2446-83-5) + (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol (168828-82-8) → 5(R)-Isoxazol-3-yloxymethyl-3-(4-morpholino-3-fluoro-phenyl)oxazolidin-2-one (252260-22-3)

Conditions	Yield
With triphenylphosphine In tetrahydrofuran	69%

4-Nitrobenzenesulfonyl chloride (98-74-8) + (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol (168828-82-8) → 4-Nitro-benzenesulfonic acid (R)-3-(3-fluoro-4-morpholin-4-yl-phenyl)-2-oxo-oxazolidin-5-ylmethyl ester (198410-26-3)

Conditions	Yield
With triethylamine

(R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol (168828-82-8) → (S)-N-[[3-[3-fluoro-4-[4-morpholinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]amine (168828-90-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: Et3N / CH2Cl2 / 4 h / 0 °C 2: NaN3 / dimethylformamide / 75 °C 3: hydrogen / Pd/C / ethyl acetate / 12 h / 760 Torr View Scheme
Multi-step reaction with 2 steps 1: Et3N 2: NH3 / methanol View Scheme
Multi-step reaction with 3 steps 1: Et3N / tetrahydrofuran / 2 h / 20 °C 2: sodium azide / dimethylformamide / 6 h / 65 °C 3: triphenylphosphine; H2O / tetrahydrofuran / 11 h / 40 °C View Scheme

(R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol (168828-82-8) → linezolid (165800-03-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: Et3N / CH2Cl2 / 4 h / 0 °C 2: NaN3 / dimethylformamide / 75 °C 3: hydrogen / Pd/C / ethyl acetate / 12 h / 760 Torr 4: pyridine View Scheme
Multi-step reaction with 3 steps 1: Et3N 2: NH3 / methanol 3: 2 h / 40 °C View Scheme
Multi-step reaction with 3 steps 1: Et3N 2: NaN3 / dimethylsulfoxide / 80 °C 3: 86 percent / Ambient temperature View Scheme

(R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol (168828-82-8) → (R)-[{N-3-(3-fluoro-4-morpholinophenyl)-2-oxo-oxazolidin-5-yl}methyl]isothiocyanate (216869-07-7)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: Et3N / tetrahydrofuran / 2 h / 20 °C 2.1: sodium azide / dimethylformamide / 6 h / 65 °C 3.1: triphenylphosphine; H2O / tetrahydrofuran / 11 h / 40 °C 4.1: Et3N / tetrahydrofuran / 4 h / 0 °C 4.2: ethyl chloroformate / tetrahydrofuran / 1 h / 0 °C View Scheme

(R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol (168828-82-8) → (S)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]methyldithiocarbamate (216868-96-1)

Conditions	Yield
Multi-step reaction with 5 steps 1: Et3N / tetrahydrofuran / 2 h / 20 °C 2: sodium azide / dimethylformamide / 6 h / 65 °C 3: triphenylphosphine; H2O / tetrahydrofuran / 11 h / 40 °C 4: Et3N / tetrahydrofuran / 7 h / 0 °C 5: Et3N / tetrahydrofuran / 0.5 h / 20 °C View Scheme

(R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol (168828-82-8) → (S)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea

Conditions	Yield
Multi-step reaction with 5 steps 1.1: Et3N / tetrahydrofuran / 2 h / 20 °C 2.1: sodium azide / dimethylformamide / 6 h / 65 °C 3.1: triphenylphosphine; H2O / tetrahydrofuran / 11 h / 40 °C 4.1: Et3N / tetrahydrofuran / 4 h / 0 °C 4.2: ethyl chloroformate / tetrahydrofuran / 1 h / 0 °C 5.1: 40 percent / NH3 / methanol / 3 h / 0 °C View Scheme

(R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol (168828-82-8) → [(S)-3-(3-Fluoro-4-morpholin-4-yl-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-dithiocarbamic acid

Conditions	Yield
Multi-step reaction with 4 steps 1: Et3N / tetrahydrofuran / 2 h / 20 °C 2: sodium azide / dimethylformamide / 6 h / 65 °C 3: triphenylphosphine; H2O / tetrahydrofuran / 11 h / 40 °C 4: Et3N / tetrahydrofuran / 7 h / 0 °C View Scheme

Upstream product

• 60456-26-0 (R)-glycidyl butyrate 
• 168828-81-7 benzyl 3-fluoro-4-(4-morpholinyl)phenylcarbamate 
• 93246-53-8 3-fluoro-4-(morpholinyl)aniline 
• 912552-56-8 ((S)-2,3-Dihydroxy-propyl)-(3-fluoro-4-morpholin-4-yl-phenyl)-carbamic acid benzyl ester 
• 912552-55-7 (3-fluoro-4-morpholin-4-yl-phenyl)-(3-oxo-propyl)-carbamic acid benzyl ester 
• 912552-54-6 (3-fluoro-4-morpholin-4-yl-phenyl)-(3-hydroxy-propyl)-carbamic acid benzyl ester 
• 369-34-6 3,4-difluoronitrobenzene 
• 2689-39-6 3-fluoro-4-(4-morpholinyl)nitrobenzene 
• 903593-93-1 N-[4(R)-(2,2-dimethyl-1,3-dioxolane-4-yl)methyl]-3-fluoro-4-morpholinylaniline 
• 32315-10-9 bis(trichloromethyl) carbonate 
• 60827-45-4 (S)-3-chloropropan-1,2-diol 
• 496031-56-2 (R)-(3-(3-fluoro-4-morpholinophenyl)-2-oxooxazolidin-5-yl)methyl acetate 
• 868405-66-7 N-[3-chloro-2-(R)-hydroxypropyl]-3-fluoro-4-(morpholin-4-yl)aniline 
• 565176-83-2 N-ethoxycarbonyl-3-fluoro-4-morpholinyl aniline 

Downstream Products

• 174649-09-3 (R)-methyl methanesulfonate 
• 198410-26-3 4-Nitro-benzenesulfonic acid (R)-3-(3-fluoro-4-morpholin-4-yl-phenyl)-2-oxo-oxazolidin-5-ylmethyl ester 
• 168828-90-8 (S)-N-[[3-[3-fluoro-4-[4-morpholinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]amine 
• 165800-03-3 linezolid 
• 168828-84-0 (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one 
• 216869-07-7 (R)-[{N-3-(3-fluoro-4-morpholinophenyl)-2-oxo-oxazolidin-5-yl}methyl]isothiocyanate 
• 216868-96-1 (S)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]methyldithiocarbamate 
• 252260-22-3 5(R)-Isoxazol-3-yloxymethyl-3-(4-morpholino-3-fluoro-phenyl)oxazolidin-2-one 
• 496031-56-2 (R)-(3-(3-fluoro-4-morpholinophenyl)-2-oxooxazolidin-5-yl)methyl acetate 
• 168828-83-9 (R)-[N-3-(3-fluoro-4-morpholinylphenyl)-2-oxo-5-oxazolidinyl]methyl 4-methylbenzenesulfonate 
• 1236077-61-4 (S)-5-((benzylamino)methyl)-3-(3-fluoro-4-morpholinophenyl)oxazolidin-2-one 
• 1334229-25-2 (S)-N-[[3-(3-fluoro-4-morpholinylphenyl)-2-oxo-5-oxazolidinyl]methyl]amine p-tolueneaulfonate salt 
• 168828-89-5 2-({(5S)-2-oxo-3-[(4-morpholino-3-fluorophenyl)]-4,5-dihydro-1,3-oxazole-5-yl}methyl)-isoindole-1,3-dione 

Relevant articles and documents

Synthesis of covalent bonding MWCNT-oligoethylene linezolid conjugates and their antibacterial activity against bacterial strains

Nowadays, infectious diseases caused by drug-resistant bacteria have become especially important. Linezolid is an antibacterial drug active against clinically important Gram positive strains; however, resistance showed by these bacteria has been reported. Nanotechnology has improved a broad area of science, such as medicine, developing new drug delivery and transport systems. In this work, several covalently bounded conjugated nanomaterials were synthesized from multiwalled carbon nanotubes (MWCNTs), a different length oligoethylene chain (Sn), and two linezolid precursors (4and7), and they were evaluated in antibacterial assays. Interestingly, due to the intrinsic antibacterial activity of the amino-oligoethylene linezolid analogues, these conjugated nanomaterials showed significant antibacterial activity against various tested bacterial strains in a radial diffusion assay and microdilution method, including Gram negative strains asEscherichia coli(11 mm, 6.25 μg mL?1) andSalmonella typhi(14 mm, ≤0.78 μg mL?1), which are not inhibited by linezolid. The results show a significant effect of the oligoethylene chain length over the antibacterial activity. Molecular docking of amino-oligoethylene linezolid analogs shows a more favorable interaction of theS2-7analog in the PTC ofE. coli.

A kind of linezolid intermediate, preparation method thereof, and method for preparing and enduring zolamide

The invention discloses a novel Linezolid intermediate, its preparation method and a novel preparation method of Linezolid, a structure of the Linezolid key intermediate is shown as a formula (I), in the formula (I), X is fluorine, chlorine, bromine or iodine. According to the invention, the Linezolid intermediate solves the problems of poor solubility of the Linezolid intermediate, and low yield and purity of the synthesized Linezolid in the prior art. The preparation methods of the invention have the advantages of easy preparation process, easy raw material acquisition, low cost, easy purification of intermediate product and final product, high yield and purity, and are suitable for large-scale industrial production.

PROCESS FOR PREPARATION OF CRYSTALLINE FORM I OF LINEZOLID AND ITS COMPOSITIONS

The present invention relates to a process for the preparation of crystalline form I of linezolid, comprising providing a solution of linezolid in a solvent, crystallizing and recovering the solid of Linezolid in crystalline form I at elevated temperature. The present invention also relates to the use of crystalline form I of linezolid prepared by the method of the present invention for preparing pharmaceutical compositions.