Triethylamine → 4-fluoro-3-hydroxy-N-methoxy-N-methylbenzamide

Participants

Reaction Conditions

Reaction Steps

To a 5 L four necked round bottom flask was added 3-hydroxy-4-fluorobenzoic acid (100 g, 0.64 mol) and CH2Cl2 (2.3 L). Triethylamine (107 mL, 0.768 mol) was then added to the suspension. The solution was cooled to ±78° C., and EDCI (184.2 g, 0.961 mol) was added portion wise followed by the addition of N,O-dimethylhydroxyamine hydrochloride (93.6 g, 0.96 mol). The reaction mixture was stirred at −78° C. for 1 h and then allowed to warm to 0° C. over a period of 2 h. The reaction mixture was transferred to a separatory funnel and washed water (2×1.2 L). The organic portion was dried over Na2SO4, filtered and concentrated in vacuo to give 4-fluoro-3-hydroxy-N-methoxy-N-methylbenzamide as a white solid (94.4 g, 74%).

Provenance & Evidence