Triethylamine → HCID 66616471, compound

Participants

Reaction Steps

To a heterogeneous mixture of 3-chloro-5-(chlorosulfonyl)-4-hydroxybenzoic acid (0.47 g, 1.8 mmol) in anhydrous dichloromethane (20 mL), at room temperature under nitrogen, was added triethylamine (0.49 mL, 3.5 mmol). To the resulting homogeneous mixture was added a solution of 1-(4′-chlorobiphenyl-3-yl)-N-(4-fluoro-benzyl)methanamine (1.1 g, 3.5 mmol) in anhydrous DCM (5 mL). The resulting mixture was stirred for 15 h before 3-chloro-5-(chlorosulfonyl)-4-hydroxybenzoic acid (0.47 g, 1.8 mmol) was added. After 3.5 h, triethylamine (0.49 mL, 3.5 mmol) was added and the reaction mixture was war wed to 40° C. After 6 h, the reaction mixture was concentrated in vacuo to remove volatiles and treated with saturated aqueous NaHCO3 solution. The resulting mixture was washed twice with Et2O and the organic washings were discarded. The aqueous layer was acidified with 1 N HCl until pH 1-2 (EMD color PHast pH 0-14 pH strips) and extracted three times with ethyl acetate. The combined organic extracts were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated in vacuo to afford an off-white solid. The crude product was purified by preparative HPLC (YMC-Pack, ODS-A, 50×500 mm, 30 minute gradient from 50% to 90% aqueous methanol with 0.1% TFA) to afford the desired compound (254 mg, 26%) as a white solid. 1H NMR (DMSO-d6) δ 13.25 (bs, 1H), 8.20 (d, J=2.0 Hz, 1H), 8.02 (d, J=2.0 Hz, 1H), 7.57-7.46 (m, 5H), 7.38-7.05 (m, 7H), 4.54 (s, 2H), 4.50 (s, 2H). MS (ESI): 558.2 (M−H)−.

Provenance & Evidence