反应详情

To a solution of ((1R,2R)-2-benzyloxy-1-hydroxymethylpropyl)carbamic acid t-butyl ester (83.1 g, CAS No. 133565-43-2) in toluene (400 mL) was added tetrabutylammonium hydrogen sulfate (24.1 g) in 50% aqueous sodium hydroxide (400 mL). t-Butylbromoacetate (125 mL) was dropwise added to the resultant solution while cooling with ice, and this solution was stirred at the same temperature for 3 hours. Then, water (500 mL) and toluene (500 mL) was added to the solution. The organic layer was separated and washed with brine. The organic layer was then dried over anhydrous magnesium sulfate. Solvent was removed by distillation under reduced pressure, to thereby obtain a crude product (122.5 g) containing ((2R,3R)-3-benzyloxy-2-t-butylcarbonylaminobutoxy)acetic acid t-butyl ester. To a solution of the obtained crude product (118g) in dichloromethane (315 mL) was added trifluoroacetic acid (315 mL), and the resultant solution was stirred for 2 hours at room temperature. Solvent was removed by distillation under reduced pressure, and the resultant product was diluted with methanol (350 mL). To the resultant solution was dropwise added thionyl chloride (96.9 mL) while cooling with ice, and then the solution was stirred for 1 hour at room temperature. Solvent was removed by distillation under reduced pressure, and the resultant product was diluted with methanol (315 mL). To the resultant solution was then dropwise added sodium methoxide (165 mL, 28% methanol solution) while cooling with ice. Solvent was removed by distillation under reduced pressure, and the resultant product was diluted with ethyl acetate and water. The organic layer was partitioned and successively washed with 1 N hydrochloric acid and brine. The organic layer was then dried over anhydrous magnesium sulfate. Solvent was removed by distillation under reduced pressure, and the resulting product was purified by silica gel column chromatography (ethyl acetate), to thereby obtain the titled compound (61.57 g). The physical properties of the compound were as follows.

1. temperaturewhile cooling with ice
2. customThe organic layer was separated
3. washwashed with brine
4. dry with materialThe organic layer was then dried over anhydrous magnesium sulfate
5. customSolvent was removed by distillation under reduced pressure
6. customto thereby obtain a crude product (122.5 g)
7. customSolvent was removed by distillation under reduced pressure
8. additionthe resultant product was diluted with methanol (350 mL)
9. temperaturewhile cooling with ice
10. stirringthe solution was stirred for 1 hour at room temperature
11. customSolvent was removed by distillation under reduced pressure
12. additionthe resultant product was diluted with methanol (315 mL)
13. temperaturedropwise added sodium methoxide (165 mL, 28% methanol solution) while cooling with ice
14. customSolvent was removed by distillation under reduced pressure
15. additionthe resultant product was diluted with ethyl acetate and water
16. customThe organic layer was partitioned
17. washsuccessively washed with 1 N hydrochloric acid and brine
18. dry with materialThe organic layer was then dried over anhydrous magnesium sulfate
19. customSolvent was removed by distillation under reduced pressure
20. customthe resulting product was purified by silica gel column chromatography (ethyl acetate)