Triethylamine → Methyl 4-hydroxy-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoate

Participants

Reaction Steps

To a solution of 1H-benzotriazole (9.11 g, 76.5 mmol) in mixed solvents (CH2Cl2/THF; 50 mL/50 mL) at room temperature was added thionylchloride (3.03 g, 25.5 mmol). After stirring for 30 min at room temperature, the mixture was treated with a solution of 2-hydroxy-5-(methoxycarbonyl)benzoic acid (5.0 g, 25.48 mmol) in THF (20 mL THF). The formation of a white precipitate was observed and the mixture was stirred for additional 1 h. The precipitate was allowed to settle and the supernatant was added to a mixture of 1,2,3,4-tetahydroisoquinoline (5.1 g, 38.3 mmol) and triethylamine (5.5 mL, 38.2 mmol) in THF (10 mL) and stirred at room temperature for 1 h. The reaction mixture was concentrate in vacuo, and the resulting crude compound was dissolved in EtOAc, washed with water, followed by 1N HCl and then brine. The organic layer was dried over Na2SO4 and concentrated in vacuo to give crude product. The crude material was purified by flash chromatography (gradient from 0% to 30% EtOAc/hexanes) to provide the title compound (5.0 g, 63%). 1H NMR (DMSO-d6, 3:1 mixture of amide rotamers) δ 10.84 (s, 1H), 7.88 (dd, J=8.8, 2.4 Hz, 1H), 7.75 (br s, 1H), 7.30-7.15 (m, 3.5H), 7.01 (d, J=8.4 Hz, 1.5H), 4.78 (br s, 1.5H), 4.41 (br s, 0.5H), 3.85-3.84 (m, 0.5H), 3.80 (s, 3H), 3.44 (br s, 1.5H), 2.86-2.80 (m, 2H); MS(ESI+) m/z 312.2 (M+H)+.

Provenance & Evidence