1289942-66-0

749927-69-3

62-57-7

1289942-66-0

The general procedure for the synthesis of 2-((3-fluoro-4-(methylcarbamoyl)phenyl)amino)-2-methylpropanoic acid from 4-bromo-2-fluoro-N-methylbenzamide and 2-aminoisobutyric acid was as follows: 4-bromo-2-fluoro-N-methylbenzamide (10 g, 43.1 mmol), 2-aminoisobutyric acid (6.7 g, 64.7 mmol), potassium carbonate ( 23.8 g, 172.4 mmol) and proline (0.7 g, 4.31 mmol) were added sequentially to a single-neck flask. Subsequently, water (1.8 ml, 100 mmol) was dissolved in DMF (60 ml) and this solution was added to the flask. Under nitrogen protection, CuCl (0.45 g, 4.31 mmol) was added to the reaction mixture, and then the reaction system was heated to 100 °C and the reaction was continuously stirred for 24 hours. After completion of the reaction, the reaction mixture was diluted with water and extracted with dichloromethane. After separation of the organic phase, the pH of the aqueous phase was adjusted to 4 with 1 mol/L citric acid solution, at which point a solid precipitated. The solid was collected by filtration and washed three times with a mixture of water and ethanol (100:1, v/v), resulting in 9.5 g of pure white solid product in 87% yield.