Hydrochloric Acid → HCID 67159370, compound

Participants

Reaction Conditions

Reaction Steps

A solution of diisopropylamine (2.97 mL, 20.85 mmol) in THF (22 mL) was stirred at 0° C. and treated dropwise with n-butyllithium (1.6 M in hexane, 13.03 mL, 20.85 mmol). The resulting solution was stirred for 5 min, and then was cooled to about −75° C. Once at the prescribed temperature, a solution of methyl 2-(4-chloro-3-(trifluoromethyl)phenyl)acetate (4.39 g, 17.38 mmol) in THF (44 mL) was added dropwise over a 15 min period. The resulting solution was stirred at about −75° C. for 30 min, and then warmed to 0° C. Once at the prescribed temperature, the solution was rapidly treated with methyl iodide (1.630 mL, 26.1 mmol). The resulting solution was stirred for 30 min, treated with 1.0 M aqueous HCl and then extracted three times with ethyl acetate. The combined organic phases were washed with 5% aqueous sodium bisulfite (2×25 mL) followed by saturated aqueous sodium chloride, dried over sodium sulfate and concentrated under vacuum. The resulting residue was purified by column chromatography on silica gel, eluting with 5-15% ethyl acetate-hexane, to provide racemic methyl 2-(4-chloro-3-(trifluoromethyl)-phenyl)propanoate as a colorless oil (3.444 g, 72%). 1H NMR (400 MHz, CDCl3) δ 7.61 (d, J=2.0 Hz, 1 H), 7.47 (d, J=8.4 Hz, 1 H), 7.42 (dd, J=8.4, 2.0 Hz, 1 H), 3.76 (q, J=7.3 Hz, 1 H), 3.68 (s, 3 H), 1.52 (d, J=7.3 Hz, 3 H).

Provenance & Evidence