To the solution of norbuprenorphine (Example 4, 0.07 g; 0.169 mmol) in N-methylpyrrolidine (1 mL) was added NaHCO3 (0.017 g; 0.203 mmol) and cyclopropylmethyl bromide (0.034 g; 0.253 mmol). The reaction mixture was placed into a pre-heated oil bath at 80° C. and stirred over 18 h. It was then diluted with water (10 mL), extracted three times with EtOAc, and the combined organic layers were washed with water (2×5 mL), brine, dried over Na2SO4 and concentrated. Column chromatography (eluent EtOAc:hexane/1:2) afforded 0.068 g (86%) of buprenorphine.
