4-Methylmorpholine → N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{(3-(1H-tetrazol-1-yl)-phenyl]oxy}acetamide

Participants

Reaction Steps

To a 25 mL recovery flask was added 3-tetrazol-1-ylphenoxyacetic acid 3 (200 mg, 0.908 mmol, 1.0 eq.) and a stirbar. 1-Ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (261 mg, 1.36 mmol, 1.5 eq.) and 1-hydroxybenzotriazole (184 mg, 1.36 mmol, 1.5 eq.) were added to the flask. DMF (10 mL) and N-methylmorpholine (300 μL, 2.72 mmol, 3.0 eq.) were added to the reaction flask. The mixture was allowed to stir for 30 min at room temperature. 5-amino-2-chlorobenzotrifluoride (355 mg, 1.82 mmol, 2.0 eq.) was added to the flask and the resulting mixture was allowed to stir overnight at room temperature. The reaction mixture was diluted with ethyl acetate (100 mL) and washed with a succession of H2O (1×50 mL), 10% aq. LiCl (3×50 mL), and sat'd aq. NaCl (1×50 mL). The aqueous phases were combined and extracted with ethyl acetate (2×30 mL). The combined organic phases were dried over anhydrous Na2SO4, filtered, and concentrated to yield an off-white solid, which did not require further purification (165 mg, 46%). LC/MSD (HP Series 1100 MSD) MS (ES+) m/z 398.0 (M+H)+1 1H-NMR, Varian 400 MHz (DMSO-d6) δ 10.55 (bs, 1H), 10.09 (s, 1H), 8.22 (d, 1H), 7.93-7.91 (m, 1H), 7.68 (d, 1H), 7.61-7.51 (m, 3H), 7.21-7.18 (m, 1H), 4.88 (s, 2H) ppm.

Provenance & Evidence