2-Bromo-4-chloro-1-fluorobenzene → tert-Butyl 4-(5-chloro-2-fluorobenzoyl)piperidine-1-carboxylate

Participants

Reaction Steps

A solution of 2-bromo-4-chloro-1-fluorobenzene (175 μL, 1.377 mmol) in THF (4.59 mL) at 78° C. was treated with n-BuLi (2.6 M, 741 μL, 1.928 mmol) and the reaction mixture was stirred for 30 min. To this was added tert-butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate (250 mg, 0.918 mmol) in one portion. The cooling bath was removed and the resulting reaction mixture was allowed to warm to rt and stirred for 1.5 h. Purification by automated flash silica gel chromatography using 10% EtOAc in hexanes afforded tert-butyl 4-(5-chloro-2-fluorobenzoyl)piperidine-1-carboxylate (287.9 mg, 92%) as a yellow oil. ESI-MS m/z [M+Na]+ 364.20.

Provenance & Evidence