Hydrochloric Acid → 5-Biphenyl-4-yl-2-methyl-3-oxo-pentanoic acid tert-butyl ester

Participants

Reaction Steps

A solution of 5-biphenyl4-yl-3-oxo-pentanoic acid tert-butyl ester (Intermediate 2, 0.30 g, 0.93 mmol) in dimethyl formamide (1.5 mL) was added to a suspension of sodium hydride (60%; 38 mg, 0.94 mmol) in dimethyl formamide (1 mL) at 0° C. under nitrogen. After stirring for 20 minutes methyl iodide (58 μL, 0.93 mmol) was added and the reaction warmed to room temperature at which stirring was continued for 2 hours. 0.5 M Hydrochloric acid (5 mL) was added and the quenched reaction mixture extracted with diethyl ether (3×5 mL). The organic phases were combined, washed with brine (5 mL) and dried (MgSO4). The volatiles were removed by evaporation under reduced pressure and the residue was purified by column chromatography on silica gel (1:6 diethyl ether: 40–60 petroleum ether) to give the title compound (163 mg, 52%) as a colourless oil. LC/MS: 3.81 min; z/e 356, calcd (M+NH4) 356. 1H NMR (400 MHz: CDCl3): 7.59 (2 H), 7.51 (2 H), 7.42 (2 H), 7.32 (1 H), 7.22 (2 H), 3.42 (1 H), 2.97 (3 H), 2.83 (1 H), 1.42 (9 H), 1.28 (3 H).

Provenance & Evidence