Triethylamine → 2-(Cyclopropylmethyl)benzoxazole-4-carboxylic acid

Participants

Reaction Steps

To an ice-cold solution of 2-cyclopropyl acetic acid (321 mg, 3.21 mmol) in dichloromethane (10 mL) was added oxalyl chloride (0.29 mL, 3.21 mmol) dropwise and a few drops of DMF. The ice bath was removed and stirring was continued for 1 h. 2-Amino-3-hydroxybenzoic acid hydrobromide (750 mg, 3.21 mmol) was added followed by triethylamine (0.90 mL, 6.42 mmol). The resulting reaction mixture was stirred at room temperature overnight. The reaction was quenched with aqueous 1 N HCl (25 mL) until the solution reached pH 1. The reaction mixture was extracted with dichloromethane. The combined organic layers were dried over Na2SO4, filtered and concentrated to a brown solid. The crude was dissolved in toluene (10 mL) and the solution was treated with p-toluenesulfonic acid monohydrate (735 mg, 3.87 mmol). The reaction mixture was then heated to reflux for 3 h. The reaction was cooled to room temperature, poured into water and extracted with ethyl acetate. The organic layer was separated, washed with water (5×50 mL) and brine, dried (Na2SO4), filtered, and concentrated. The crude was purified by recrystallization from diethyl ether and hexanes to afford 2-(cyclopropylmethyl)benzoxazole-4-carboxylic acid (441 mg, 63%) as a light brown solid: 1H NMR (500 MHz, DMSO-d6) δ 13.04 (br s, 1H), 7.94 (dd, J=8.1, 0.9 Hz, 1H), 7.81 (dd, J=7.8, 0.9 Hz, 1H), 7.45 (t, J=7.9 Hz, 1H), 2.92 (d, J=7.0 Hz, 2H), 1.27-1.16 (m, 1H), 0.60-0.54 (m, 2H), 0.36-0.30 (m, 2H); MS (ESI+) m/z 218 (M+H).

Provenance & Evidence