反应详情

A 50% sodium hydroxide solution (400 mL) and tetrabutylammoniumbisulfate (24.1 g) were added to a toluene (400 mL) solution of ((1R,2R)-2-benzyloxy-1-hydroxymethylpropyl) carbamic acid t-butyl ester (83.1 g, CAS#133565-43-2). Under ice-cooling, t-butyl bromoacetic acid ester (125 mL) was added dropwise, and stirring was continued for 3 hours at the same temperature. Water (500 mL) and toluene (500 mL) were added, and the organic layer was partitioned, and the resultant was washed with brine. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was removed under a vacuum, and a crude material (122.5 g) containing ((2R,3R)-3-benzyloxy-2-t-butoxycarbonylaminobutoxy)acetic acid t-butyl ester was obtained. Dichloromethane (315 mL) and trifluoroacetic acid (315 mL) were added to the obtained crude material (118 q), and stirring was continued for 2 hours at room temperature. The solvent was removed under a vacuum, and methanol (350 mL) was added. Under ice-cooling, thionyl chloride (96.9 mL) was added dropwise, and the resultant was stirred at room temperature for 1 hour. The solvent was removed under a vacuum, and methanol (315 mL) was added, and under ice-cooling, sodium methoxide (165 mL, 28% methanol solution) was added dropwise. The solvent was removed under a vacuum, and ethyl acetate and water were added, and the organic layer was partitioned. The organic layer was washed with 1 N hydrochloric acid and brine in sequence, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was removed under a vacuum, and the resultant was purified by silica gel column chromatography (ethyl acetate), and the title compound (61.57 g) was obtained. The physical property values are as follows.

1. temperatureUnder ice-cooling
2. customthe organic layer was partitioned
3. washthe resultant was washed with brine
4. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
5. customthe solvent was removed under a vacuum
6. additiona crude material (122.5 g) containing ((2R,3R)-3-benzyloxy-2-t-butoxycarbonylaminobutoxy)acetic acid t-butyl ester
7. customwas obtained
8. customobtained crude material (118 q)
9. stirringstirring
10. waitwas continued for 2 hours at room temperature
11. customThe solvent was removed under a vacuum, and methanol (350 mL)
12. additionwas added
13. temperatureUnder ice-cooling
14. additionthionyl chloride (96.9 mL) was added dropwise
15. stirringthe resultant was stirred at room temperature for 1 hour
16. customThe solvent was removed under a vacuum, and methanol (315 mL)
17. additionwas added
18. temperatureunder ice-cooling
19. additionsodium methoxide (165 mL, 28% methanol solution) was added dropwise
20. customThe solvent was removed under a vacuum, and ethyl acetate and water
21. additionwere added
22. customthe organic layer was partitioned
23. washThe organic layer was washed with 1 N hydrochloric acid and brine in sequence
24. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
25. customThe solvent was removed under a vacuum
26. customthe resultant was purified by silica gel column chromatography (ethyl acetate)