Hydrochloric Acid → (4S)-4-benzyl-3-[(2R)-2-[[4-(trifluoromethyl)phenyl]methyl]butanoyl]oxazolidin-2-one

Participants

Reaction Conditions

Reaction Steps

To a 3-necked 5 L RBF is added THF (2 L) and (4S)-4-benzyl-3-butanoyl-oxazolidin-2-one (270 g 1.09 moles) under N2. The resulting solution is cooled to −68° C. in an acetone-dry ice bath. To the cold solution is added sodium bis(trimethylsilyl)amide (1320 mL of 1M THF solution; 1.32 moles) dropwise over 1.5 h while the internal temperature is held between −68 to −60° C. Upon completion of the addition, the reaction is stirred at −68° C. for 30 min. To the cold solution is then added 4-trifluoromethylbenzyl bromide (278 g; 1.16 moles) in THF (1 L) over 30 min at −68° C. After 1.5 h, the reaction is poured into 1 M HCl. The mixture is extracted with ethyl acetate (3 L×1). The extracts are combined and washed with aq. NaHCO3 (2 L×1) and brine (2 L×1). The organic phase is dried over Na2SO4, filtered, and concentrated. The solid is triturated with EtOH (600 mL) at 15° C. Filtration provides the title compound as a solid (270 g, MS:[M+H]+=406 m/z).

Provenance & Evidence