N-bromobutanimide → HCID 90220120, compound

Participants

Reaction Steps

To a solution of [(R)-1-(4-cyano-thiazol-2-yl)-piperidin-3-yl]-carbamic acid tert-butyl ester (13.0 g, 42.2 mmol) in N,N-dimethylformamide (250 mL) was added N-bromosuccinimide (8.25 g, 46. mmol) and the mixture was stirred under argon at ambient temperature for 30 minutes. Analysis by thin layer chromatography (silica stationary phase eluted with 25% v/v ethyl acetate in hexanes) indicated clean conversion of [(R)-1-(4-cyano-thiazol-2-yl)-piperidin-3-yl]-carbamic acid tert-butyl ester in to a slightly less polar compound. The reaction mixture was poured into water (1 L) and extracted with ethyl acetate (3×250 mL), the combined organic extracts were washed with brine (2×200 mL), dried over sodium sulfate, filtered and concentrated in vacuo to give an off-white solid. The crude product was triturated with 1:1 v/v diethyl ether/petroleum ether (300 mL total volume). [(R)-1-(5-Bromo-4-cyano-thiazol-2-yl)-piperidin-3-yl]-carbamic acid tert-butyl ester was obtained as a colorless solid by filtration, washing with 1:2 v/v diethyl ether/petroleum ether and drying by passage of air (14.33 g, 88%). An additional amount of [(R)-1-(5-bromo-4-cyano-thiazol-2-yl)-piperidin-3-yl]-carbamic acid tert-butyl ester was obtained by purification of the residue obtained from concentration of the mother liquors by chromatography using a silica gel column gradient eluted from 5% up to 40% v/v ethyl acetate in hexanes. The product containing fractions were combined and concentrated in vacuo to obtain additional [(R)-1-(5-bromo-4-cyano-thiazol-2-yl)-piperidin-3-yl]-carbamic acid tert-butyl ester as a colorless solid (1.18 g, 7%).

Provenance & Evidence