反应详情

Methyl 5-(benzyloxycarbonylamino)-3-oxopentanoate (4.5 g, 15.3 mmoles) is dissolved in anhydrous tetrahydrofuran (25 mL) and this solution is added slowly dropwise to an ice-cooled solution of lithium borohydride in anhydrous tetrahydrofuran (2 M, 25 mL, 50 mmoles). When the addition is complete, the cooling bath is removed and the reaction is stirred at ambient temperature for 16 hours. The clear, colorless solution is again cooled in an ice bath, and aqueous hydrochloric acid (1 M, 50 mL) is added slowly dropwise to decompose the excess reducing agent (gas is evolved). When a homogeneous solution is obtained, the mixture is concentrated to remove tetrahydrofuran. Ethyl acetate (100 mL) is added; the mixture is shaken well and poured into a separatory funnel. The layers are allowed to separate and the bottom aqueous layer is drawn off. The aqueous layer is then washed twice more with ethyl acetate (100 mL each), and the combined ethyl acetate solutions are washed with saturated aqueous sodium chloride (50 mL). The ethyl acetate solution is then dried over anhydrous sodium sulfate, filtered and evaporated to a pale brown syrup. The crude product is purified on silica gel (200 mL bed volume) eluting with ethyl acetate (500 mL) then ethyl acetate:methanol (99:1 [v/v], 500 mL then 95:5 [v/v], 1000 mL). Fractions containing pure product by thin layer chromatography are pooled and evaporated to a pale yellow oil. The oil is dried well in vacuo. The yield is 3.6 g (92%). The oil solidifies on standing at 4° C.

1. additionWhen the addition
2. customthe cooling bath is removed
3. temperatureThe clear, colorless solution is again cooled in an ice bath
4. additionaqueous hydrochloric acid (1 M, 50 mL) is added slowly dropwise
5. customWhen a homogeneous solution is obtained
6. concentrationthe mixture is concentrated
7. customto remove tetrahydrofuran
8. additionEthyl acetate (100 mL) is added
9. stirringthe mixture is shaken well
10. additionpoured into a separatory funnel
11. customto separate
12. washThe aqueous layer is then washed twice more with ethyl acetate (100 mL each)
13. washthe combined ethyl acetate solutions are washed with saturated aqueous sodium chloride (50 mL)
14. dry with materialThe ethyl acetate solution is then dried over anhydrous sodium sulfate
15. filtrationfiltered
16. customevaporated to a pale brown syrup
17. customThe crude product is purified on silica gel (200 mL bed volume)
18. washeluting with ethyl acetate (500 mL)
19. additionFractions containing pure product by thin layer chromatography
20. customevaporated to a pale yellow oil
21. customThe oil is dried well in vacuo
22. customon standing at 4° C.