1-Bromo-3-chlorobenzene → (R)-Tert-butyl 3-(3-chlorobenzoyl)piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of 1-bromo-3-chlorobenzene (54.3 g, 0.286 mol) in anhydrous THF (500 mL) at −78° C. under nitrogen was added drop wise a solution of 2.5 M n-BuLi in hexane (114 mL, 0.286 mol). After stirring for 1 hr at −78° C., a solution of (R)-tert-butyl 3-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate (65.8 g, 0.242 mol) in anhydrous THF (300 mL) was added drop wise. After addition, the reaction mixture was allowed to warm to room temperature and stirred for 2 h. TLC indicated the reaction was complete. The mixture was quenched with saturated NH4Cl solution (300 mL) and extracted with ethyl acetate (3×200 mL). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuo to give the crude product (R)-tert-butyl 3-(3-chlorobenzoyl)piperidine-1-carboxylate (92 g, 100%), which was used immediately for next step without purification.

Provenance & Evidence