O-Xylene → (S)-4-[2-(4,4-Diethylcyclohexyl)-4-(3-methoxypiperidin-1-yl)phenyl]piperazine-1-carboxylic acid t-butyl ester

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-[4-bromo-2-(4,4-dimethylcyclohexyl)phenyl]piperazine-1-carboxylic acid t-butyl ester (153 mg, 0.32 mmol) produced in Example (38c), (S)-3-methoxypiperidine hydrochloride (72.8 mg, 0.48 mmol) produced in Example (50a), sodium t-butoxide (200 mg, 2.08 mmol), palladium(II) acetate (14.4 mg, 0.064 mmol), tri-t-butylphosphonium tetrafluoroborate (57.7 mg, 0.192 mmol) and xylene (4 mL) was stirred for 6 hours and 10 minutes at an external temperature of 100° C. under a nitrogen atmosphere. To the reaction mixture were further added sodium t-butoxide (100 mg, 1.04 mmol), palladium(II) acetate (7.2 mg, 0.032 mmol) and tri-t-butylphosphonium tetrafluoroborate (27.9 mg, 0.096 mmol), followed by stirring for 1 hour at an external temperature of 100° C. under a nitrogen atmosphere. The reaction mixture was air-cooled to room temperature and then purified by NH silica gel column chromatography (ethyl acetate/hexane) to give 59 mg of the title compound as a brown oil.

Provenance & Evidence