1-Hydroxybenzotriazole → 2-[3-fluoro-4-(methylsulfanyl)phenyl]-N-methoxy-N-methyl-3-(tetrahydro-2H-pyran-4-yl)propanamide

Participants

Reaction Steps

A solution of N-methoxymethanamine hydrochloride (467 mg) in acetonitrile (16 mL) was neutralized with triethylamine (1.82 mL), and 2-[3-fluoro-4-(methylsulfanyl)phenyl]-3-(tetrahydro-2H-pyran-4-yl)propanoic acid (1.30 g), N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (918 mg) and 1-hydroxybenzotriazole (73.4 mg) were added under ice-cooling. The reaction mixture was warmed to room temperature and stirred overnight. The reaction mixture was diluted with ethyl acetate, and washed with water and saturated aqueous sodium hydrogen carbonate. The ethyl acetate layer was dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography, and the title compound (1.33 g, yield 89%) was obtained as a colorless amorphous solid from a fraction eluted with ethyl acetate-hexane (9:1, volume ratio).

Provenance & Evidence