Dimethylformamide → 2-Formyl-5-(trifluoromethyl)benzoic acid

Participants

Reaction Steps

To a solution of n-butyl lithium (56.0 ml, 140 mmol) in tetrahydrofuran (100 mL) at −78° C. was added a solution of 2-bromo-5-(trifluoromethyl)benzoic acid (17.9 g, 66.7 mmol) in tetrahydrofuran (100 mL) over 0.5 hour, at which time the solution turned dark red. After stirring for 1 hour, N,N-dimethylformamide (50 mL, 646 mmol) was added dropwise and the reaction mixture was allowed to warm to room temperature over 6 hours. The mixture was cooled to 0° C. and then a solution of 2 N sodium hydroxide (120 mL) was added. The mixture was extracted with ether (2×50 mL). The aqueous layer was separated and concentrated hydrochloric acid was added to it until the pH was acidic. The mixture was extracted with ethyl acetate (3×80 mL). The organic extracts were combined, dried with sodium sulfate, filtered, and concentrated. The residue was purified on Analogix® Intelliflash280™ (SiO2, 7-100% solvent A in hexanes, solvent A=3:1:0.1 hexane:ethyl aceate:acetic acid) over 1 hour to obtain the title compound (4.5 g, 20.6 mmol, 31% yield). 1H NMR (300 MHz, DMSO-d6) δ ppm 6.78 (br, 1H) 7.93 (d, J=8.48 Hz, 1H) 8.13-8.20 (m, 2H) 8.38 (br, 1H); MS (DCI/NH3) m/z 236 (M+NH4)+.

Provenance & Evidence