反应详情

DMF (three drops) and oxalyl chloride (3.50 mL, 40.0 mmol) were added to a methylene chloride (35 mL) solution of 4-(3,3,3-trifluoropropoxy)benzoic acid (4.68 g, 20.0 mmol) obtained in preparation process of Example 33 (33a), under ice-cooling with stirring. The mixture was stirred at room temperature for 3.5 hours, and then the solvent was evaporated. The obtained residue was dissolved in THF (20 mL). This solution and a 1 M sodium hydroxide aqueous solution (20 mL) were added dropwise simultaneously under ice-cooling with stirring to a solution mixture of a 1 M sodium hydroxide aqueous solution (40 mL) of 2-amino-3-[4-(trifluoromethoxy)phenyl]propanoic acid hydrochloride (5.71 g, 20.0 mmol) prepared in Reference Example 2, water (20 mL), and THF (15 mL). The resulting mixture was stirred under ice-cooling for 70 minutes, and then the solvents (mainly THF) were evaporated. Water was added to the residue, and the resulting mixture was changed to acidic by adding 2 M hydrochloric acid thereto. The precipitated crystalline solid was collected by filtration, washed with water and n-hexane, and dried under reduced pressure to give 8.75 g of the title compound (white powder, yield: 94%).

1. temperaturecooling
2. stirringThe mixture was stirred at room temperature for 3.5 hours
3. customthe solvent was evaporated
4. dissolutionThe obtained residue was dissolved in THF (20 mL)
5. additionThis solution and a 1 M sodium hydroxide aqueous solution (20 mL) were added dropwise simultaneously under ice-
6. temperaturecooling
7. stirringThe resulting mixture was stirred under ice-
8. temperaturecooling for 70 minutes
9. customthe solvents (mainly THF) were evaporated
10. additionWater was added to the residue
11. additionby adding 2 M hydrochloric acid
12. filtrationThe precipitated crystalline solid was collected by filtration
13. washwashed with water and n-hexane
14. customdried under reduced pressure