1-Aminocyclopropane-1-carboxylic acid → 1-(4-(Methylcarbamoyl)-3-fluorophenylamino)cyclopropanecarboxylic acid

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 4-bromo-2-fluoro-N-methylbenzamide (6.4 g, 27.5 mmol), 1-aminocyclopropanecarboxylic acid (4.29 g, 42.4 mmol), CuI (1.047 g, 5.5 mmol), K2CO3 (9.50 g, 68.0 mmol), in DMF (64 mL) was added H2O (6.4 mL), triethylamine (0.164 mL, 1.1 mmol) followed by 2-acetyl cyclohexanone (0.717 g, 5.10 mmol). The reaction mixture was stirred at 100° C. overnight. The reaction was monitored by TLC and LCMS. H2O was added, and the aqueous layer was washed with ethyl acetate. The aqueous layer was acidified with 1M citric acid solution (pH˜4) and extracted with ethyl acetate. The organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and crystallized with DCM to afford 3.01 g of the title compound as an off-white solid.

Provenance & Evidence