Hydrogen Bromide → (R)-2-Bromo-1-[4-phenylmethoxy-3-[(methylsulfonyl)amino]phenyl]ethanol

Participants

Reaction Steps

A 25 mL round bottom flask with magnetic stirbar and toluene-filled Dean-Stark trap with reflux condenser and gas bubbler, was charged with (R)-α,α-diphenyl-2-pyrrolidinemethanol (1.13 g, 4.46 mmol) and trimethylboroxine (418 μL, 2.99 mmol) in toluene (11 mL) under N2. The reaction was stirred at ambient for ~30 minutes and then heated to reflux for 2.75 hours. Upon cooling, this solution was added to a stirred ~13° C. THF (185 mL) solution under N2 containing 2-bromo-1-[4-phenylmethoxy-3-[(methylsulfonyl)amino]phenyl]ethanone (14.25 g, 36 mmol) prepared as described in step F of Example 1. To this was added 5.2 mL of 10.1M BH3 -Me2S/THF (52 mmol) over ~5 minutes, keeping T≤-11.6° C. Upon completion of the reaction, HBr was bubbled through the solution until the pH was ~1 whereupon a solution of 50 mL MeOH in 100 mL methyl tert-butyl ether was carefully added. The mixture was washed with H2O (4×100 mL=400 mL) (until final wash had pH~4-5), diluted with EtOAc (50 mL), dried over Na2SO4. After solvent removal in vacuo, 12.84 g (90%) of crude title compound was obtained in 86% purity with an ee of 96.9%.

Provenance & Evidence