2,5-Dimethoxybenzoyl chloride → Methyl 3-(2,5-dimethoxyphenyl)-2-(3-methoxy-4-(trifluoromethyl)phenyl)-3-oxopropanoate

Participants

Reaction Conditions

Reaction Steps

To a solution of methyl 2-(3-methoxy-4-(trifluoromethyl)phenyl)acetate (18.6 g, 75 mmol) in anhydrous THF (250 mL) at −78° C., LiHMDS (1.0 M in THF, 79 mL, 79 mmol) was added dropwise under N2. The resulting mixture was stirred at −78° C. for 30 minutes, and a solution of 2,5-dimethoxybenzoyl chloride (15.9 g, 78 mmol; intermediate in Intermediate 1) in anhydrous THF (50 mL) was added dropwise. The reaction mixture was stirred for another 1 h at −78° C., quenched with saturated aqueous NH4Cl (100 mL), and extracted with ethyl acetate (2×100 mL). The combined organic layers were dried over anhydrous sodium sulfate and concentrated under vacuum to give the title compound (30.1 g). 1H NMR (DMSO-d6): δ 7.50 (d, 1H), 7.34 (d, 1H), 7.09-7.07 (m, 1H), 6.94-6.87 (m, 3H), 5.71 (s, 1H), 3.92 (s, 3H), 3.85 (s, 3H), 3.77 (s, 3H), 3.65 (s, 3H).

Provenance & Evidence