Aminoisobutyric acid → 4-(2-Carboxypropan-2-ylamino)-2-fluorobenzoic acid

Participants

Reaction Conditions

Reaction Steps

4-Bromo-2-fluorobenzoic acid (20 g, 91.3 mmol), 2-aminoisobutyric acid (14.5 g, 140 mmol), CuI (3.47 g, 18.22 mmol) and K2CO3 (31.56 g, 227.91 mmol) were mixed in DMF (200 mL), H2O (20 mL) and TEA (0.63 mL, 4.54 mmol). To the reaction mixture was then added 2-acetyl cyclohexanone (2.4 g, 17.1 mmol). The reaction mixture was stirred at 90° C. for 14 h. After completion of the reaction water was added. Aqueous layer was washed with ethyl acetate. Aqueous layer was made acidic by adding 1M citric acid solution (pH˜4). The product was extracted with ethyl acetate (3×200 mL). Combined organic layer was dried over anhydrous Na2SO4, and concentrated under reduced pressure to afford 16 g of 4-(2-carboxypropan-2-ylamino)-2-fluorobenzoic acid as crude product. This crude material was used as such for the next example.

Provenance & Evidence