Hexane → (R)-tert-butyl 3-(2-(benzyloxy)-3,5-difluorobenzoyl)piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-(benzyloxy)-1-bromo-3,5-difluorobenzene (13.7 g, 46 mmol) in anhydrous THF (100 mL) at −78° C. under nitrogen was added dropwise a solution of 2.5 M n-BuLi in hexane (18.4 mL, 46 mmol). After stirring for 1 hr at −78° C., a solution of (R)-tert-butyl 3-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate (10.43 g, 38.3 mmol) in anhydrous THF (40 mL) was added dropwise. After addition, the reaction mixture was allowed to warm to rt and stirred for 2 h. The mixture was quenched with saturated NH4Cl solution (100 mL) and extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography on silica gel eluting with AcOEt/hexane (1:20→1:10) to provide (R)-tert-butyl 3-(2-(benzyloxy)-3,5-difluorobenzoyl)piperidine-1-carboxylate (6.4 g, 32%) as a light yellow oil.

Provenance & Evidence