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

Participants

Reaction Conditions

Reaction Steps

A solution of 546 g of 3-[2-(2-fluorophenyl)-1-oxoethyl]-4(R)-phenyl-2-oxazolidinone in 2,180 mL of peroxide-free tetrahydrofuran is cooled to an internal temperature of -5 to -8° C. A solution of 1,773 mL of lithium hexamethyldisilazide in tetrahydrofuran (1M) is added over a period of 55 minutes, while maintaining an internal temperature of 0 to -5° C. The solution is stirred at an internal temperature of 0 to -5° C. for 1 hour and then cooled to an internal temperature of -20° C. 150 mL of Bromoacetonitrile is added over a period of 40 minutes, while maintaining an internal temperature of -15 to -20° C. The reaction mixture is stirred at an internal temperature of -15 to -20° C. for 4.5 hours and added to a solution of 478 g of NaCl in 2,164 mL of water and 214 g of concentrated HCl cooled to an internal temperature of 0 to 5° C., over a period of 20 minutes, while maintaining the internal temperature below 9° C. After addition of 500 mL of tetrahydrofuran, the slurry is stirred for 15 minutes at an internal temperature of 5 to 8° C., and then warmed to room temperature (17 to 19° C.) over a period of 30 minutes. The organic layer is separated and washed with a solution of 632 g of NaCl in 2,180 mL of water. The slurry is stirred for 15 minutes, the organic layer is separated and concentrated under reduced pressure (20 mm Hg; bath temperature 45° C.) to a final volume of 1.4-1.6L. 2,500 mL of t-Butyl methyl ether is added and the slurry is vigorously stirred for 1 hour at room temperature (18 to 20° C.). The solid is collected and washed with 2×150 mL of t-butyl methyl ether and dried at 45 to 50° C. (20 mm Hg) for 20 hours to obtain β-(R)-(2-fluorophenyl)-γ,2-dioxo-4(R)-phenyl-3-oxazolidinebutyronitrile as an off-white crystalline solid.

Provenance & Evidence