Bromoacetonitrile → beta-(R)-(2-fluorophenyl)-gamma,2-dioxo-4(R)-phenyl-3-oxazolidinebutyronitrile

Participants

Reaction Conditions

Reaction Steps

To a solution of 3-[(2-fluorophenyl)-acetyl]-4(R)-phenyl-2-oxazolidinone (435 g, 1.45 mol) in THF (6000 mL), is added sodium hexamethyldisilazide [(TMS)2NNa, 1M in THF, 1480 ml, 1.48 mol] dropwise at -78° C. The resulting mixture is then warmed to -30° C. and stirred for 2.5 hours. After this time the reaction mixture is recooled to -78° C. and a solution of BrCH2CN (175 g, 1.46 mmol) in THF (200 mL) is added. The reaction mixture is then warmed to -40° C. and stirred for 2 hours. Subsequently the resulting solution is treated with saturated NH4Cl (1×3000 ml) and extracted with EtOAc (1×3000 mL). The organic layer is separated, washed with H2O (1×1500 mL), saturated NaCl solution (2×1500 mL), dried over MgSO4 and concentrated in vacuo, to provide 3-[(R)-β-cyano-α-(2-fluorophenyl)-propionyl]-4-(R)-phenyl-2-oxazolidinone, m.p. 179-181° C.

Provenance & Evidence