Dimethyl Sulfate → N-t-butoxycarbonyl(3,5-difluorophenyl)alanine methyl ester

Participants

Reaction Steps

N-t-butoxycarbonyl(3,5-difluorophenyl)alanine (2.6 g, 8.6 mmol) in 35 mL of dry THF under nitrogen is stirred with 2.0 g (14.5 mmol) of pulverized K2CO3 and 1.0 mL (10.5 mmol) of dimethylsulfate at 40° C. for 17 h. The mixture is diluted with ethyl acetate, washed twice with 1 N KH2PO4, once with 1 N NaHCO3, twice with water, and finally with brine. The organic phase is dried with Na2SO4 and concentrated to a sticky solid. Trituration with heptane affords 2.32 g (7.4 mmol, 85%) of N-t-butoxycarbonyl(3,5-difluorophenyl)alanine methyl ester as a white solid. 1H NMR (CDCl3) δ 6.72-6.56 (m, 3H), 5.04 (d, J=8 Hz, 1H), 4.57 (q, J=6 Hz, 1H), 3.75 (s, 3H), 3.14 (dd, J=6, 14 Hz, 1H), 3.01 (dd, J=6, 14 Hz, 1H), 1.43 (s, 9H).

Provenance & Evidence