168828-84-0

Basic information

• Product Name: (R)-5-(Azidomethyl)-3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxazolidinone
• Synonyms: (R)-5-(Azidomethyl)-3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxazolidinone;DeacetaMide Linezolid Azide;(5R)-5-(AzidoMethyl)-3-[3-fluoro-4-(4-Morpholinyl)phenyl]-2-oxazolidinone;(R)-5-(AzidoMethyl)-3-[3-fluoro-4-(4-Morpholinyl)phenyl]-;Linezolid Related CoMpound A;2-Oxazolidinone,5-(azidoMethyl)-3-[3-fluoro-4-(4-Morpholinyl)phenyl]-,(5R)-;Linezolid USP RC A;(R)-5-(azidomethyl)-3-(3-fluoro-4-morpholinophenyl)oxazolidin-2-one
• CAS NO: 168828-84-0
• Molecular Formula: C₁₄H₁₆FN₅O₃
• Molecular Weight: 321.31
• EINECS: 1312995-182-4
• Product Categories: Aromatics;Chiral Reagents;Heterocycles;Impurities;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 168828-84-0.mol
• Article Data: 25

Chemical Properties

• Melting Point: 102.5-103.5 °C
• Appearance: /
• Storage Temp.: -20°C Freezer
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• CAS DataBase Reference: (R)-5-(Azidomethyl)-3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxazolidinone(CAS DataBase Reference)
• NIST Chemistry Reference: (R)-5-(Azidomethyl)-3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxazolidinone(168828-84-0)
• EPA Substance Registry System: (R)-5-(Azidomethyl)-3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxazolidinone(168828-84-0)

Safety Data

• Hazardous Substances Data: 168828-84-0(Hazardous Substances Data)

Usage

Uses

Different sources of media describe the Uses of 168828-84-0 differently. You can refer to the following data:
1. An impurity of Linezolid (L466500), as antimycobacterial agent.
2. An impurity of Linezolid (L466500), as antimycobacterial agent. Linezolid USP Related Compound A.

InChI:InChI=1/C14H17FN5O3/c1-18(17-16)12-9-20(14(21)23-12)11-4-2-3-10(15)13(11)19-5-7-22-8-6-19/h2-4,12H,5-9H2,1H3/q+1/t12-/m1/s1

Synthetic route

(R)-methyl methanesulfonate (174649-09-3) → (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0)

Conditions	Yield
With sodium azide In N,N-dimethyl-formamide at 85℃;	97.23%
With sodium azide In N,N-dimethyl-formamide at 60℃; Reflux;	95%
With sodium azide In tetrahydrofuran; water for 8h; Reflux;	93%

(S)-N-[[3-[3-fluoro-4-[4-morpholinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]amine (168828-90-8) → (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0)

Conditions	Yield
With fluorosulfonyl azide; potassium hydrogencarbonate In tert-butyl methyl ether; water; N,N-dimethyl-formamide at 20℃; for 0.0833333h;	92%

(R)-[N-3-(3-fluoro-4-morpholinylphenyl)-2-oxo-5-oxazolidinyl]methyl 4-methylbenzenesulfonate (168828-83-9) → (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0)

Conditions	Yield
With sodium azide In N,N-dimethyl-formamide at 80 - 85℃; for 4h;	90%

(5R)-5-(chloromethyl)-3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxazolidinone → (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0)

Conditions	Yield
With sodium azide In N,N-dimethyl-formamide at 85℃; for 12h;	87%
With sodium azide In N,N-dimethyl-formamide at 85℃; for 12h;	86%

(R)-5-azidomethyl-1,3-oxazolidin-2-one (677726-40-8) + 4-(2-fluoro-4-bromophenyl)morpholine (513068-89-8) → (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0)

Conditions	Yield
With copper(l) iodide; potassium carbonate; rac-diaminocyclohexane In 1,4-dioxane at 110℃; for 23h;	84%

(S)-3-azido-1-chloropropan-2-yl 3-fluoro-4-morpholinophenylcarbamate (1373348-81-2) → (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0)

Conditions	Yield
With potassium carbonate In acetone at 20℃; for 8h;	83%

(R)-5-azidomethyl-1,3-oxazolidin-2-one (677726-40-8) + 4-(2-fluoro-4-iodophenyl)morpholine (1250999-09-7) → (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0)

Conditions	Yield
With trans-1,2-Diaminocyclohexane; potassium carbonate; copper(l) chloride In 1,4-dioxane at 110℃; for 15h; Inert atmosphere; Darkness;	82%
With potassium carbonate; trans-1,2-Diaminocyclohexane; copper(l) chloride In 1,4-dioxane at 110℃; for 15h; Inert atmosphere; Darkness; Sealed vessel;	82%

(S)-3-azido-1-chloropropan-2-yl chloroformate (1373348-78-7) + 3-fluoro-4-(morpholinyl)aniline (93246-53-8) → (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0)

Conditions	Yield
With potassium carbonate In acetone at 20℃;	82%

(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

(R)-N-(3-fluoro-4-morpholinylphenyl)oxiranylmethyl carbamic acid ethyl ester (1223581-08-5) → (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0)

Conditions	Yield
With sodium azide; ammonium chloride In methanol; water at 80 - 85℃; for 4h;	76%

3-chloro-2-((phenoxycarbonyl)oxy)propyl azide (881012-11-9) + 3-fluoro-4-(morpholinyl)aniline (93246-53-8) → (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0)

Conditions	Yield
With N-benzyl-N,N,N-triethylammonium chloride; potassium carbonate In N,N-dimethyl-formamide at 80℃; for 12h;

3-(3-fluoro-4-morpholin-4-yl-phenylamino)-propan-1-ol → (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0)

Conditions	Yield
Multi-step reaction with 6 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 5.1: Et3N / CH2Cl2 / 4 h / 0 °C 6.1: NaN3 / dimethylformamide / 75 °C View Scheme

(3-fluoro-4-morpholin-4-yl-phenyl)-(3-oxo-propyl)-carbamic acid benzyl ester (912552-55-7) → (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0)

Conditions	Yield
Multi-step reaction with 4 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 3.1: Et3N / CH2Cl2 / 4 h / 0 °C 4.1: NaN3 / dimethylformamide / 75 °C View Scheme

(3-fluoro-4-morpholin-4-yl-phenyl)-(3-hydroxy-propyl)-carbamic acid benzyl ester (912552-54-6) → (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0)

Conditions	Yield
Multi-step reaction with 5 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 4.1: Et3N / CH2Cl2 / 4 h / 0 °C 5.1: NaN3 / dimethylformamide / 75 °C View Scheme

((S)-2,3-Dihydroxy-propyl)-(3-fluoro-4-morpholin-4-yl-phenyl)-carbamic acid benzyl ester (912552-56-8) → (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: 96 percent / sodium hydride / tetrahydrofuran / 0 °C 2: Et3N / CH2Cl2 / 4 h / 0 °C 3: NaN3 / dimethylformamide / 75 °C View Scheme

3-fluoro-4-(morpholinyl)aniline (93246-53-8) → (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0)

Conditions	Yield
Multi-step reaction with 7 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 6.1: Et3N / CH2Cl2 / 4 h / 0 °C 7.1: NaN3 / dimethylformamide / 75 °C View Scheme
Multi-step reaction with 3 steps 1: Et3N / tetrahydrofuran / 2 h / 20 °C 2: sodium azide / dimethylformamide / 6 h / 65 °C View Scheme
Multi-step reaction with 4 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 3: 35.423 g / triethylamine / CH2Cl2 / 20 h 4: sodium azide / dimethylformamide / 16 h / 75 °C View Scheme

3,4-difluoronitrobenzene (369-34-6) → (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0)

Conditions	Yield
Multi-step reaction with 5 steps 1: N,N-diisopropylethylamine / acetonitrile / 17 h / Heating 2: H2 / PtO2 / methanol / 3 h / 20 °C / 1471.02 Torr 3: Et3N / tetrahydrofuran / 2 h / 20 °C 4: sodium azide / dimethylformamide / 6 h / 65 °C View Scheme
Multi-step reaction with 6 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 5: 35.423 g / triethylamine / CH2Cl2 / 20 h 6: sodium azide / dimethylformamide / 16 h / 75 °C View Scheme
Multi-step reaction with 6 steps 1.1: methanol / 25 - 30 °C 2.1: hydrogen / palladium 10% on activated carbon / methanol / 20 - 30 °C / Autoclave 3.1: sodium carbonate / toluene; acetone / 0 - 5 °C 4.1: butan-1-ol; n-butyllithium / hexane; tetrahydrofuran / -15 - 30 °C / Inert atmosphere 4.2: -10 - 15 °C 5.1: triethylamine / dichloromethane / 20 - 30 °C 6.1: sodium azide / N,N-dimethyl-formamide / 60 °C / Reflux View Scheme

3-fluoro-4-(4-morpholinyl)nitrobenzene (2689-39-6) → (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: H2 / PtO2 / methanol / 3 h / 20 °C / 1471.02 Torr 2: Et3N / tetrahydrofuran / 2 h / 20 °C 3: sodium azide / dimethylformamide / 6 h / 65 °C View Scheme
Multi-step reaction with 5 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 4: 35.423 g / triethylamine / CH2Cl2 / 20 h 5: sodium azide / dimethylformamide / 16 h / 75 °C View Scheme
Multi-step reaction with 5 steps 1.1: hydrogen / palladium 10% on activated carbon / methanol / 20 - 30 °C / Autoclave 2.1: sodium carbonate / toluene; acetone / 0 - 5 °C 3.1: butan-1-ol; n-butyllithium / hexane; tetrahydrofuran / -15 - 30 °C / Inert atmosphere 3.2: -10 - 15 °C 4.1: triethylamine / dichloromethane / 20 - 30 °C 5.1: sodium azide / N,N-dimethyl-formamide / 60 °C / Reflux View Scheme

(5R)-3-[3-fluoro-4-(4-morpholinyl)phenyl]-5-carbaldehyde-2-oxazolidinone → (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: NaBH4 / methanol / 0 °C 2: Et3N 3: NaN3 / dimethylsulfoxide / 80 °C 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)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0)

Conditions	Yield
Multi-step reaction with 6 steps 1: CH2Cl2 / Ambient temperature 2: 2N HCl / Ambient temperature 3: lead tetraacetate (LTA) / tetrahydrofuran / 0 °C 4: NaBH4 / methanol / 0 °C 5: Et3N 6: NaN3 / dimethylsulfoxide / 80 °C View Scheme

C28H32F2N4O8 (239438-43-8) → (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: lead tetraacetate (LTA) / tetrahydrofuran / 0 °C 2: NaBH4 / methanol / 0 °C 3: Et3N 4: NaN3 / dimethylsulfoxide / 80 °C View Scheme

C31H36F2N4O8 (239438-39-2) → (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0)

Conditions	Yield
Multi-step reaction with 5 steps 1: 2N HCl / Ambient temperature 2: lead tetraacetate (LTA) / tetrahydrofuran / 0 °C 3: NaBH4 / methanol / 0 °C 4: Et3N 5: NaN3 / dimethylsulfoxide / 80 °C View Scheme

benzyl 3-fluoro-4-(4-morpholinyl)phenylcarbamate (168828-81-7, 1027135-00-7) → (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) n-butyllithium / 1.) THF, hexane, -78 deg C, 35 min, 2.) THF, hexane, -78 deg C, 1 h 2: 35.423 g / triethylamine / CH2Cl2 / 20 h 3: sodium azide / dimethylformamide / 16 h / 75 °C View Scheme
Multi-step reaction with 3 steps 1.1: butan-1-ol; n-butyllithium / hexane; tetrahydrofuran / -15 - 30 °C / Inert atmosphere 1.2: -10 - 15 °C 2.1: triethylamine / dichloromethane / 20 - 30 °C 3.1: sodium azide / N,N-dimethyl-formamide / 60 °C / Reflux View Scheme
Multi-step reaction with 3 steps 1.1: n-butyllithium / hexane; tetrahydrofuran / 3.5 h / -78 °C / Inert atmosphere 1.2: -78 - 20 °C 1.3: 0.17 h / 20 °C 2.1: triethylamine / dichloromethane / 18 h / 0 - 20 °C 3.1: sodium azide / N,N-dimethyl-formamide / 4 h / 80 - 85 °C View Scheme
Multi-step reaction with 3 steps 1.1: n-butyllithium / tetrahydrofuran / -78 °C 1.2: -78 - 20 °C 2.1: triethylamine / dichloromethane 3.1: sodium azide / N,N-dimethyl-formamide / 70 °C View Scheme
Multi-step reaction with 3 steps 1.1: n-butyllithium / tetrahydrofuran / -30 - -20 °C 1.2: -30 - 50 °C 2.1: triethylamine / dichloromethane / 0 - 5 °C 3.1: sodium azide / N,N-dimethyl-formamide / 2 h / 25 - 85 °C View Scheme

C8H10FNO3S (1201594-21-9) → (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: bis(1,5-cyclooctadiene)nickel(0); sodium t-butanolate; 1,3-bis[2,6-diisopropylphenyl]imidazolium chloride / 1,4-dioxane / 3 h / 80 °C / Inert atmosphere 2.1: N-iodo-succinimide; trifluoroacetic acid / 14 h / 23 °C / Inert atmosphere 2.2: 23 °C 3.1: trans-1,2-Diaminocyclohexane; potassium carbonate; copper(l) chloride / 1,4-dioxane / 15 h / 110 °C / Inert atmosphere; Darkness View Scheme
Multi-step reaction with 3 steps 1: sodium t-butanolate / bis(1,5-cyclooctadiene)nickel (0); 1,3-bis[(2,6-diisopropyl)phenyl]imidazolinium chloride / 1,4-dioxane / 3 h / 80 °C / Inert atmosphere; Sealed vessel 2: trifluoroacetic acid; N-iodo-succinimide / 14 h / 23 °C / Inert atmosphere; Sealed vessel 3: potassium carbonate / trans-1,2-Diaminocyclohexane; copper(l) chloride / 1,4-dioxane / 15 h / 110 °C / Inert atmosphere; Darkness; Sealed vessel View Scheme

phenyl N,N-dimethylsulfamate (66950-63-8) → (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0)

Conditions

Yield

Multi-step reaction with 4 steps 1.1: Inert atmosphere 2.1: bis(1,5-cyclooctadiene)nickel(0); sodium t-butanolate; 1,3-bis[2,6-diisopropylphenyl]imidazolium chloride / 1,4-dioxane / 3 h / 80 °C / Inert atmosphere 3.1: N-iodo-succinimide; trifluoroacetic acid / 14 h / 23 °C / Inert atmosphere 3.2: 23 °C 4.1: trans-1,2-Diaminocyclohexane; potassium carbonate; copper(l) chloride / 1,4-dioxane / 15 h / 110 °C / Inert atmosphere; Darkness View Scheme

N-(2-fluorophenyl)-morpholine → (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: N-iodo-succinimide; trifluoroacetic acid / 14 h / 23 °C / Inert atmosphere 1.2: 23 °C 2.1: trans-1,2-Diaminocyclohexane; potassium carbonate; copper(l) chloride / 1,4-dioxane / 15 h / 110 °C / Inert atmosphere; Darkness View Scheme
Multi-step reaction with 2 steps 1: trifluoroacetic acid; N-iodo-succinimide / 14 h / 23 °C / Inert atmosphere; Sealed vessel 2: potassium carbonate / trans-1,2-Diaminocyclohexane; copper(l) chloride / 1,4-dioxane / 15 h / 110 °C / Inert atmosphere; Darkness; Sealed vessel View Scheme

phenol (108-95-2) → (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: Inert atmosphere 2.1: Inert atmosphere 3.1: bis(1,5-cyclooctadiene)nickel(0); sodium t-butanolate; 1,3-bis[2,6-diisopropylphenyl]imidazolium chloride / 1,4-dioxane / 3 h / 80 °C / Inert atmosphere 4.1: N-iodo-succinimide; trifluoroacetic acid / 14 h / 23 °C / Inert atmosphere 4.2: 23 °C 5.1: trans-1,2-Diaminocyclohexane; potassium carbonate; copper(l) chloride / 1,4-dioxane / 15 h / 110 °C / Inert atmosphere; Darkness View Scheme

N-ethoxycarbonyl-3-fluoro-4-morpholinyl aniline (565176-83-2) → (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: n-butyllithium / hexane; tetrahydrofuran / 3.5 h / -78 °C / Inert atmosphere 1.2: -78 - 20 °C 1.3: 0.5 h / 20 °C 2.1: triethylamine / dichloromethane / 18 h / 0 - 20 °C 3.1: sodium azide / N,N-dimethyl-formamide / 4 h / 80 - 85 °C View Scheme

2-fluorophenol (367-12-4) → (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0)

Conditions

Yield

Multi-step reaction with 4 steps 1: sodium hydride / 1,2-dimethoxyethane; mineral oil / 15 h / 23 °C / Inert atmosphere 2: sodium t-butanolate / bis(1,5-cyclooctadiene)nickel (0); 1,3-bis[(2,6-diisopropyl)phenyl]imidazolinium chloride / 1,4-dioxane / 3 h / 80 °C / Inert atmosphere 3: trifluoroacetic acid; N-iodo-succinimide / 14 h / 23 °C / Inert atmosphere; Sealed vessel 4: potassium carbonate / trans-1,2-Diaminocyclohexane; copper(l) chloride / 1,4-dioxane / 15 h / 110 °C / Inert atmosphere; Darkness; Sealed vessel View Scheme

2-fluorophenyl diethylcarbamate (459408-52-7) → (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0)

Conditions

Yield

Multi-step reaction with 3 steps 1: sodium t-butanolate / bis(1,5-cyclooctadiene)nickel (0); 1,3-bis[(2,6-diisopropyl)phenyl]imidazolinium chloride / 1,4-dioxane / 3 h / 80 °C / Inert atmosphere 2: trifluoroacetic acid; N-iodo-succinimide / 14 h / 23 °C / Inert atmosphere; Sealed vessel 3: potassium carbonate / trans-1,2-Diaminocyclohexane; copper(l) chloride / 1,4-dioxane / 15 h / 110 °C / Inert atmosphere; Darkness; Sealed vessel View Scheme

(R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0) → (S)-N-[[3-[3-fluoro-4-[4-morpholinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]amine (168828-90-8)

Conditions	Yield
With water; triphenylphosphine In tetrahydrofuran at 70℃;	100%
With hydrogen In methanol at 40 - 60℃; under 3750.38 Torr; for 3h; Temperature; Pressure; Reagent/catalyst; Autoclave;	98%
With palladium on activated charcoal; hydrogen; acetic acid In methanol for 2h;	81%

(R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0) + thioacetic acid (507-09-5) → linezolid (165800-03-3)

Conditions	Yield
Stage #1: (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one; tiolacetic acid at 23℃; for 7h; Stage #2: With potassium hydroxide In water at 23℃;	90%
at 23℃; for 7h; Inert atmosphere;	90%
Ambient temperature;	86%
at 20℃; for 15h;	85%
at 20℃; for 15h;

C33H52N2O10 + (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0) → C48H70FN7O13

Conditions	Yield
With copper(l) iodide; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃; for 4h;	86%

acetic anhydride (108-24-7) + (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0) → linezolid (165800-03-3)

Conditions	Yield
With palladium on activated charcoal; hydrogen In methanol at 20℃; under 1034.32 Torr; for 3h;	85%
With hydrogen; palladium 10% on activated carbon In dichloromethane under 1103.36 Torr; for 6h;	80%
Stage #1: acetic anhydride; (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one With hydrogen; acetic acid; palladium 10% on activated carbon In ethyl acetate at 25 - 35℃; under 1551.49 Torr; for 3h; Stage #2: With sodium carbonate In water; ethyl acetate for 0.166667h; Product distribution / selectivity;	78%

ethylenesulfonyl fluoride (677-25-8) + (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0) → PH-027

Conditions	Yield
In ethyl acetate at 100℃; for 16h; Sealed tube;	85%

C40H69NO13 (677726-20-4) + (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0) → C54H85FN6O16

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; copper(l) iodide In tetrahydrofuran at 20℃; for 2h;	80%

N-(3,6,9,12-tetraoxapentadec-14-ynyl)-2,3,3a,4,7,7a-hexahydro-1,3-dioxo-4,7-methano-isoindol (1308299-12-8) + (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0) → (R)-1-(1-(1-((3-(3-fluoro-4-morpholinophenyl)-2-oxooxazolidin-5-yl)methyl)-1H-1,2,3-triazol-4-yl)-2,5,8,11-tetraoxatridecan-13-yl)-2,3,3a,4,7,7a-hexahydro-1,3-dioxo-4,7-methanoisoindole (1309042-01-0)

Conditions	Yield
With copper(l) iodide; triethylamine In acetonitrile at 20℃; for 2h; Inert atmosphere;	75%

(R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0) + acetylene (74-86-2) → PH-027

Conditions	Yield
In 1,2-dimethoxyethane at 90℃; for 12h;	74%

dimethyl acetylenedicarboxylate (762-42-5) + (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0) → 1-[3-(3-fluoro-4-morpholin-4-yl-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-1H-[1,2,3]triazole-4,5-dicarboxylic acid dimethyl ester (503026-28-6)

Conditions	Yield
In 1,2-dimethoxyethane at 90℃; for 24h;	73%

3-butyn-1-yl p-toluenesulfonate (23418-85-1) + (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0) → C25H28FN5O6S (677726-23-7)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; copper(l) iodide In tetrahydrofuran at 20℃; for 2h;	63%

methyl ethynyl ketone (1423-60-5) + (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0) → (R)-5-(5-Acetyl-[1,2,3]triazol-1-ylmethyl)-3-(3-fluoro-4-morpholin-4-yl-phenyl)-oxazolidin-2-one + (R)-5-(4-Acetyl-[1,2,3]triazol-1-ylmethyl)-3-(3-fluoro-4-morpholin-4-yl-phenyl)-oxazolidin-2-one (503026-25-3)

Conditions	Yield
In 1,2-dimethoxyethane at 90℃; for 24h;	A 5% B 62%

C33H57NO10 (677726-42-0) + (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0) → C47H73FN6O13

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; copper(l) iodide In tetrahydrofuran at 20℃; for 15h;	56%

3,6,9,12-tetraoxapentadec-14-yn-1-ol (87450-10-0) + (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0) → (R)-3-(3-fluoro-4-morpholinophenyl)-5-((4-(13-hydroxy-2,5,8,11-tetraoxatridecyl)-1H-1,2,3-triazol-1-yl)methyl)oxazolidin-2-one (1308299-13-9)

Conditions	Yield
With copper(l) iodide; triethylamine In acetonitrile at 20℃; for 2h; Inert atmosphere;	54%

2-(N-methyl-N-prop-2-yn-1-ylamino)ethanol (13105-72-1) + (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0) → C20H27FN6O4

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; copper(l) iodide In tetrahydrofuran at 20℃; for 16h;	50.6%

C43H78N2O12 (677727-50-3) + (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0) → C57H94FN7O15

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; copper(l) iodide In tetrahydrofuran at 20℃; for 4h;	50%

C42H74N2O12 + (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0) → C56H90FN7O15

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; copper(l) iodide In tetrahydrofuran at 20℃; for 4h;	50%

C42H76N2O13 (677727-53-6) + (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0) → C56H92FN7O16

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; copper(l) iodide In tetrahydrofuran at 20℃; for 4h;	50%

pent-1-yn-5-ol (5390-04-5) + (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0) → C19H24FN5O4

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; copper(l) iodide In tetrahydrofuran at 20℃; for 16h;	48.7%

1,11-bis(2-propyn-1-oxy)-3,6,9-trioxaundecane (159428-42-9) + (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0) → C42H54F2N10O11 (1308299-19-5)

Conditions	Yield
With copper(l) iodide; triethylamine In acetonitrile at 20℃; for 2h; Inert atmosphere;	47%

4-amino-1-(3,6,9,12-tetraoxapentadec-14-ynyl)pyrimidin-2(1H)-one (1308299-10-6) + (R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one (168828-84-0) → (R)-5-((4-(13-(4-amino-2-oxopyrimidin-1(2H)-yl)-2,5,8,11-tetraoxatridecyl)-1H-1,2,3-triazol-1-yl)methyl)-3-(3-fluoro-4-morpholinophenyl)oxazolidin-2-one (1308299-15-1)

Conditions	Yield
With copper(l) iodide; triethylamine In acetonitrile at 20℃; for 2h; Inert atmosphere;	46%

Upstream product

• 881012-11-9 3-chloro-2-((phenoxycarbonyl)oxy)propyl azide 
• 93246-53-8 3-fluoro-4-(morpholinyl)aniline 
• 1223581-08-5 (R)-N-(3-fluoro-4-morpholinylphenyl)oxiranylmethyl carbamic acid ethyl ester 
• 677726-40-8 (R)-5-azidomethyl-1,3-oxazolidin-2-one 
• 1250999-09-7 4-(2-fluoro-4-iodophenyl)morpholine 
• 1201594-21-9 C₈H₁₀FNO₃S 
• 66950-63-8 phenyl N,N-dimethylsulfamate 
• 108-95-2 phenol 
• 168828-90-8 (S)-N-[[3-[3-fluoro-4-[4-morpholinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]amine 
• 105-58-8 Diethyl carbonate 
• 530-62-1 1,1'-carbonyldiimidazole 
• 224323-51-7 3-fluoro-4-(morpholin-4-yl)-phenyl isocyanate 
• 459408-52-7 2-fluorophenyl diethylcarbamate 
• 367-12-4 2-fluorophenol 

Downstream Products

• 503026-25-3 (R)-5-(4-Acetyl-[1,2,3]triazol-1-ylmethyl)-3-(3-fluoro-4-morpholin-4-yl-phenyl)-oxazolidin-2-one 
• 503026-28-6 1-[3-(3-fluoro-4-morpholin-4-yl-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-1H-[1,2,3]triazole-4,5-dicarboxylic acid dimethyl ester 
• 165800-03-3 linezolid 
• 677726-23-7 C₂₅H₂₈FN₅O₆S 
• 1170353-87-3 (R)-3-(3-fluoro-4-morpholinophenyl)-5-((5-methyl-1H-1,2,3-triazol-1-yl)methyl)oxazolidin-2-one 
• 1170353-86-2 (R)-3-(3-fluoro-4-morpholinophenyl)-5-((4-methyl-1H-1,2,3-triazol-1-yl)methyl)oxazolidin-2-one 
• 912359-80-9 (S)-[3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]aminomethane 
• 1430414-17-7 C₂₀H₁₉F₄N₃O₅S 
• 1430414-18-8 C₂₀H₂₀F₃N₃O₅S 
• 1430414-06-4 C₂₀H₂₁ClFN₃O₅S 
• 1430414-16-6 C₂₀H₂₀Cl₂FN₃O₅S 
• 1430414-15-5 C₂₀H₂₀ClF₂N₃O₅S 
• 1430414-14-4 C₁₈H₂₀FN₃O₅S₂ 
• 1430414-13-3 C₂₁H₂₁F₄N₃O₅S 

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.

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

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