Hydrochloric Acid → Rofecoxib

Participants

Reaction Steps

To a solution of phenylacetic acid (27.4 g, 201 mmol) and 2-bromo-1-(4-(methylsulfonyl)phenyl)ethanone (Step 1) (60 g, 216 mmol, 1.075 eq.) in acetonitrile (630 mL) at 25° C. was added slowly Et3N (30.8 mL, 1.1 eq.). The mixture was stirred for 20 min. at r.t. and then cooled in an ice bath. DBU (60.1 mL, 3 eq.) was slowly added. After stirring for 20 min. in the ice bath, the reaction was complete and the mixture was acidified with 1N HCl (color changed from dark brown to yellow). Then 2.4 L of ice and H2O were added, the mixture was stirred for a few minutes, and the precipitate was filtered and rinsed with H2O, giving 64 g of crude wet product. The solid was dissolved in 750 mL of CH2Cl2, dried over MgSO4, filtered and 300 g of silica gel was added to the filtrate. The solvent was evaporated to near dryness (silica gel a bit sticky), the residue was applied on top of a silica gel plug in a sintered glass funnel and eluted with 10% EtOAc/CH2Cl2, giving after evaporation of the solvent and swishing in EtOAc, 36.6 g (58%) of the title compound.

Provenance & Evidence