反应详情

1,1-Cyclopropanedicarboxylic acid (50 g) was dissolved in acetonitrile (500 ml) under a nitrogen atmosphere, and N-methylimidazole (31 ml) was added dropwise with stirring and cooling in an ice water bath. After stirring at the same temperature for 30 minutes, thionyl chloride (29 ml) was added dropwise. After stirring at the same temperature for 30 minutes, a mixed solution of benzyl alcohol (45.7 g) and N-methylimidazole (31 ml) was added with cooling in an ice water bath, and the reaction mixture was stirred at the same temperature for 6 hours. A 2N aqueous solution of sodium hydroxide (900 ml) was added to adjust pH 8. tert-Butyl methyl ether (500 ml) was added to the resultant solution, and the mixture was stirred. The organic layer and the aqueous layer were separated, and the organic layer was extracted with a 5% aqueous solution of sodium hydrogencarbonate (200 ml). The aqueous layers were combined, cooled in an ice water bath, and 5N hydrochloric acid (300 ml) was added to adjust pH 4. Ethyl acetate (1000 ml) was added, and the mixture was stirred for a while. The organic layer was separated, washed with brine, and dried over anhydrous sodium sulfate. The residue obtained by distilling off the solvent was dissolved in methanol (120 ml), and water (120 ml) was added dropwise with stirring at room temperature. After stirring at room temperature for 30 minutes, and with cooling in an ice water bath for 2 hours, the precipitated solid was suction filtered, and washed with water (60 ml, twice). The resultant solid was dried under reduced pressure at 40° C. to give the title compound (59 g, 69%).

1. temperaturecooling in an ice water bath
2. stirringAfter stirring at the same temperature for 30 minutes
3. stirringAfter stirring at the same temperature for 30 minutes
4. temperaturewith cooling in an ice water bath
5. stirringthe reaction mixture was stirred at the same temperature for 6 hours
6. stirringthe mixture was stirred
7. customThe organic layer and the aqueous layer were separated
8. extractionthe organic layer was extracted with a 5% aqueous solution of sodium hydrogencarbonate (200 ml)
9. temperaturecooled in an ice water bath
10. addition5N hydrochloric acid (300 ml) was added
11. additionEthyl acetate (1000 ml) was added
12. stirringthe mixture was stirred for a while
13. customThe organic layer was separated
14. washwashed with brine
15. dry with materialdried over anhydrous sodium sulfate
16. customThe residue obtained
17. distillationby distilling off the solvent
18. dissolutionwas dissolved in methanol (120 ml)
19. additionwater (120 ml) was added dropwise
20. stirringwith stirring at room temperature
21. stirringAfter stirring at room temperature for 30 minutes
22. temperaturewith cooling in an ice water bath for 2 hours
23. filtrationfiltered
24. washwashed with water (60 ml
25. customThe resultant solid was dried under reduced pressure at 40° C.