反应详情

1,1-Cyclopropanedicarboxylic acid (2.5 g) was dissolved in tetrahydrofuran (25 ml) under a nitrogen atmosphere, triethylamine (2.68 ml) was added dropwise thereto while stirring in an ice water bath. After stirring at the same temperature for 30 min, thionyl chloride (1.4 ml) was added dropwise while stirring in an ice water bath. After stirring at the same temperature for 30 min, a solution of 2-fluoroaniline (2.04 ml) in tetrahydrofuran (15 ml) was added while stirring in an ice water bath, and the reaction mixture was allowed to gradually warm up to room temperature and stirred overnight. To the reaction mixture was added a 2N aqueous solution of sodium hydroxide (75 ml), and tetrahydrofuran was removed under reduced pressure. To the resultant aqueous solution was added tert-butyl methyl ether (25 ml) and stirred. The organic layer and aqueous layer were separated. The aqueous layer was cooled in an ice water bath, 5N hydrochloric acid (30 ml) was added and stirred. The precipitated solid was collected by filtration and washed with water. Drying under aeration and hot-air drying at 60° C. for 8 hr provided the titled compound as white powder (2.294 g, 54%).

1. stirringAfter stirring at the same temperature for 30 min
2. stirringwhile stirring in an ice water bath
3. stirringAfter stirring at the same temperature for 30 min
4. stirringwhile stirring in an ice water bath
5. stirringstirred overnight
6. customwas removed under reduced pressure
7. additionTo the resultant aqueous solution was added tert-butyl methyl ether (25 ml)
8. stirringstirred
9. customThe organic layer and aqueous layer were separated
10. temperatureThe aqueous layer was cooled in an ice water bath
11. addition5N hydrochloric acid (30 ml) was added
12. stirringstirred
13. filtrationThe precipitated solid was collected by filtration
14. washwashed with water
15. customDrying under aeration
16. customhot-air drying at 60° C. for 8 hr