Methanol → HCID 58017418, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of (R)-tert-butyl 3-(3-methylbenzoyl)piperidine-1-carboxylate (168 g, 0.55 mol) in anhydrous THF (600 mL) at −15° C. under nitrogen was added dropwise a solution of 1 M R-CBS-oxazaborolidine in toluene (82 mL, 82 mmol, 0.15 eq). After stirring for 1 hr at −15° C., a solution of 10 M BH3 in THF (60 mL, 0.60 mol, 1.1 eq) was added dropwise. After addition, the reaction mixture was stirred for 2 hr at −15° C. TLC indicated the starting material was disappeared. Methanol (400 mL) was added dropwise carefully at −15° C. The solvent was removed under reduced pressure, the residue was purified by column chromatography on silica gel eluting with EtOAc/hexane (1:30→1:15) to provide the light yellow oil (95 g, HPLC≧70%, ratio≧3:1). The mixture was dissolved in EtOAc until the alcohol was just dissolved (about 5 mL/1 g), the solvent was removed on the rotary evaporator until a few crystals appeared. The solution was cooled to rt slowly and stood for 1-2 hr. To the above solution was added hexane (about 300 mL) and then filtered, the crystals were washed with cool hexane and re-crystallized two more times to afford the pure isomer (R)-tert-butyl 3-((S)-hydroxy(m-tolyl)methyl)piperidine-1-carboxylate (20 g, ee≧99%).

Provenance & Evidence