N-[[(2S)-oxiran-2-yl]methyl]acetamide

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The product of Step 1 (0.20 g, 0.88 mmol) is dissolved into EtOAc (30 mL) in a Parr bottle and 10% Pd/C (100 mg) added under nitrogen. The mixture is hydrogenated on a Parr apparatus for 2 hrs at 30 psi. Filtration and evaporation of solvent gave a white solid. This material is added to a mixture of N-[(2S)oxiranylmethyl] acetamide (0.81 g, 7.0 mmol) and magnesium trifluoromethanesulfonate (0.42 g, 1.3 mmol) in dry CH3CN (10 mL) at room temperature. After 20 hrs solvent is evaporated and the residue purified by chromatography (4%MeOH/CH2Cl2) to give a foamy solid (0.23 g, 79%). HRMS (FAB) calcd for C13H19N3O4S +H1 314.1174, found 314.1174. added under nitrogen Filtration and evaporation of solvent gave a white solid After 20 hrs solvent is evaporated the residue purified by chromatography (4%MeOH/CH2Cl2)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Phenylmethyl [3-fluoro-4-[tetrahydro-1,1-dioxido-2-(2-propenyl)-2H-1,2-thiazin-4-yl]phenyl]carbamate (1.70 g, 4.07 mmol) is dissolved in dry THF (18 ml) under nitrogen and cooled to −78°. A 1.6 M solution of n-butyl lithium (2.7 ml, 4.32 mmol) in hexane is added and stirred for 1 hr. A solution of N-[(2S)oxiranylmethyl]acetamide 11 (960 mg, 8.35 mmol) in dry THF (6.5 ml) is added and the stirred mixture allowed to come to 25° overnight. Solvent is evaporated and the residue partitioned between chloroform (100 ml) and ammonium chloride solution (50 ml). The organic layer is washed with brine (40 ml), dried (MgSO4) and evaporated. The residue is chromatographed over silica gel (150 g) eluting with 2-4% methanol-chloroform to afford the oxazolidinone as a white foam (1.275 g, 73%). HRMS(FAB) calcd for m+H=426.1499: Found; 426.1506. cooled to −78° to come to 25° overnight Solvent is evaporated the residue partitioned between chloroform (100 ml) and ammonium chloride solution (50 ml) The organic layer is washed with brine (40 ml) dried (MgSO4) evaporated The residue is chromatographed over silica gel (150 g) eluting with 2-4% methanol-chloroform

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Phenylmethyl [3-fluoro-4-[tetrahydro-1,1-dioxido-2-(2-propenyl)-2H-1,2-thiazin-4-yl]phenyl]carbamate (1.70 g, 4.07 mmol) is dissolved in dry THF (18 ml) under nitrogen and cooled to −78°. A 1.6 M solution of n-butyl lithium (2.7 ml, 4.32 mmol) in hexane is added and stirred for 1 hr. A solution of N-[(2S)oxiranylmethyl]acetamide 11 (960 mg, 8.35 mmol) in dry THF (6.5 ml) is added and the stirred mixture allowed to come to 25° overnight. Solvent is evaporated and the residue partitioned between chloroform (100 ml) and ammonium chloride solution (50 ml). The organic layer is washed with brine (40 ml), dried (MgSO4) and evaporated. The residue is chromatographed over silica gel (150 g) eluting with 2-4% methanol-chloroform to afford the oxazolidinone as a white foam (1.275 g, 73%). HRMS(FAB) calcd for m+H=426.1499: Found; 426.1506. cooled to −78° to come to 25° overnight Solvent is evaporated the residue partitioned between chloroform (100 ml) and ammonium chloride solution (50 ml) The organic layer is washed with brine (40 ml) dried (MgSO4) evaporated The residue is chromatographed over silica gel (150 g) eluting with 2-4% methanol-chloroform

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Phenylmethyl [3-fluoro-4-[tetrahydro-1,1-dioxido-2-(2-propenyl)-2H-1,2-thiazin-4-yl]phenyl]carbamate (1.70 g, 4.07 mmol) is dissolved in dry THF (18 ml) under nitrogen and cooled to −78°. A 1.6 M solution of n-butyl lithium (2.7 ml, 4.32 mmol) in hexane is added and stirred for 1 hr. A solution of N-[(2S)oxiranylmethyl]acetamide 11 (960 mg, 8.35 mmol) in dry THF (6.5 ml) is added and the stirred mixture allowed to come to 25° overnight. Solvent is evaporated and the residue partitioned between chloroform (100 ml) and ammonium chloride solution (50 ml). The organic layer is washed with brine (40 ml), dried (MgSO4) and evaporated. The residue is chromatographed over silica gel (150 g) eluting with 24% methanol-chloroform to afford the oxazolidinone as a white foam (1.275 g, 73%). HRMS(FAB) calcd for m+H=426.1499; Found: 426.1506. cooled to −78° to come to 25° overnight Solvent is evaporated the residue partitioned between chloroform (100 ml) and ammonium chloride solution (50 ml) The organic layer is washed with brine (40 ml) dried (MgSO4) evaporated The residue is chromatographed over silica gel (150 g) eluting with 24% methanol-chloroform

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The product of Step 1 (0.20 g, 0.88 mmol) is dissolved into EtOAc (30 mL) in a Parr bottle and 10% Pd/C (100 mg) added under nitrogen. The mixture is hydrogenated on a Parr apparatus for 2 hrs at 30 psi. Filtration and evaporation of solvent gave a white solid. This material is added to a mixture of N-[(2S)oxiranylmethyl] acetamide (0.81 g, 7.0 mmol) and magnesium trifluoromethanesulfonate (0.42 g, 1.3 mmol) in dry CH3CN (10 mL) at room temperature. After 20 hrs solvent is evaporated and the residue purified by chromatography (4%MeOH/CH2Cl2) to give a foamy solid (0.23 g, 79%). HRMS (FAB) calcd for C13H19N3O4S +H1 314.1174, found 314.1174. added under nitrogen Filtration and evaporation of solvent gave a white solid After 20 hrs solvent is evaporated the residue purified by chromatography (4%MeOH/CH2Cl2)