反应详情

温度

10 °C

Into a one-liter four-necked flask were poured 43.9 g (0.125 mole) of (3R)-5-benzyloxycarbonylamino-3-(2-tetrahydropyranyloxy)pentanoic acid (2-c) obtained in the above process B and 290 ml of acetonitrile. Furthermore, 19.6 g (0.121 mole) of N,N'-carbonyldiimidazole was added to the contents over a period of 15 minutes in a nitrogen stream with stirring. Gas evolution was observed. Approximately 30 minutes later the gas evolution was nearly complete. Then, the contents were cooled to approximately 10° C., and 35.2 g (0.178 mole) of potassium malonate tert-butyl ester and next 11.4 g (0.119 mole) of magnesium chloride were separately added thereto. After stirring for 1 hour at the same temperature, the contents were heated to 50° C. and allowed to react for 2 hours. After removing acetonitrile by distillation, 150 ml of ethyl acetate and 200 ml of a 5 wt % aqueous hydrochloric acid solution were added to thereby adjust the pH to 4.5. After separating the aqueous layer, the organic layer was neutralized by adding 25 ml of a 5 wt % aqueous sodium bicarbonate solution. The organic layer was washed with saturated sodium chloride solution and then dried with magnesium sulfate. The solvent was then removed by distillation, to thereby obtain 72.3 g of a crude oily product. The crude product was purified with a silica gel column using hexane/ethyl acetate=1/1 as an eluent to obtain the intended oily product (1). The yield was 57.8 g (79%).

1. customApproximately 30 minutes
2. stirringAfter stirring for 1 hour at the same temperature
3. temperaturethe contents were heated to 50° C.
4. customto react for 2 hours
5. customAfter removing acetonitrile
6. distillationby distillation, 150 ml of ethyl acetate and 200 ml of a 5 wt % aqueous hydrochloric acid solution
7. additionwere added
8. customAfter separating the aqueous layer
9. additionby adding 25 ml of a 5 wt % aqueous sodium bicarbonate solution
10. washThe organic layer was washed with saturated sodium chloride solution
11. dry with materialdried with magnesium sulfate
12. customThe solvent was then removed by distillation
13. customto thereby obtain 72.3 g of a crude oily product
14. customThe crude product was purified with a silica gel column