Hydrochloric Acid → Tert-butyl 5-biphenyl-4-yl-3-oxopentanoate

Participants

Reaction Steps

A solution of t-butyl acetoaceate (1.84 mL, 11.1 mmol) in tetrahydrofuran (20 mL) was added to a stirred suspension of sodium hydride (488 mg, 12.2 mmol) in tetrahydrofuran (10 mL) at 0° C. under nitrogen. After stirring for 10 minutes n-butyl lithium (1.6 M in hexanes; 7.3 mL, 11.6 mmol) was added dropwise over 2 minutes then stirring was continued for a further 10 minutes. A solution of 4-bromomethyl-biphenyl (Intermediate 1, 3.00 g, 12.2 mmol) in tetrahydrofuran (6 mL) was added dropwise over 10 minutes and the resulting solution stirred at 0° C. for 1.5 hours. 6 M Hydrochloric acid (15 mL) was added then the crude reaction mixture was extracted with diethyl ether (3×50 mL). The organic phases were combined, washed with brine (50 mL), dried (MgSO4) then the solvent evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (1:20 diethyl ether:cyclohexane) to give the title compound (1.37 g, 38%) as a yellow solid. LC/MS: 3.78 min; z/e 342, calcd (M+NH4) 342. 1H NMR (400 MHz: CDCl3): 7.55 (2 H), 7.50 (2 H), 7.43 (2 H), 7.32 (1 H), 7.25 (2 H), 3.34 (2 H), 2.95 (4 H), 1.45 (9 H).

Provenance & Evidence