p-Toluenesulfonic acid → Ethyl 4-((3,3-dimethylcyclobutyl)(quinolin-3-ylamino) methyl)benzoate

Participants

Reaction Conditions

Reaction Steps

A flask containing ethyl 4-(3,3-dimethylcyclobutanecarbonyl)benzoate (397 mg, 1.53 mmol) was charged with toluene (13.9 mL), quinolin-3-amine (200 mg, 1.39 mmol), and para-toluene sulfonic acid (26.8 mg, 0.139 mmol). The reaction was refluxed with a Dean-Stark for 24 h. The reaction was quenched with water and extracted three times with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, and concentrated to give 508 mg of crude material. To this crude material was added anhydrous methanol (6.47 mL) and the solution was cooled to 0° C. Sodium borohydride (147 mg, 3.88 mmol) was then added. After 5 h, the reaction was partly concentrated and quenched with saturated aqueous ammonium chloride. The reaction mixture was extracted three times with ethyl acetate. The combined organic layers were then dried over sodium sulfate, filtered, and concentrated to give 560 mg of crude material. Purification by column chromatography (0-50% ethyl acetate in heptane) provided ethyl 4-((3,3-dimethylcyclobutyl)(quinolin-3-ylamino)methyl)benzoate (17.0 mg, 3.4% yield) as an oil. 1H NMR (400 MHz, CDCl3) δ: 8.47 (d, J=2.9 Hz, 1H), 8.03-7.97 (m, 2H), 7.90-7.86 (m, 1H), 7.46-7.42 (m, 2H), 7.42-7.30 (m, 3H), 6.69 (d, J=2.7 Hz, 1H), 4.40-4.31 (m, 2H), 4.27 (dd, J=9.2, 4.3 Hz, 1H), 2.58-2.47 (m, 1H), 2.03 (ddd, J=11.2, 7.6, 4.2 Hz, 1H), 1.79-1.67 (m, 2H), 1.67-1.55 (m, 1H), 1.36 (t, J=7.1 Hz, 3H), 1.14 (s, 3H), 1.09 (s, 3H). MS (M+1): 389.3.

Provenance & Evidence