反应详情

(S)-5-(2-Methylpropyl)-3-morpholinone, 3 g (0.019 mol), is suspended in a solution of 50 ml of concentrated hydrochloric acid and 50 ml of water, refluxed for four hours, cooled to room temperature, and extracted with 200 ml of dichloromethane. The aqueous layer is separated, evaporated in vacuo, the residue dissolved in 200 ml of water and the pH adjusted with a 10% aqueous solution of sodium hydroxide to pH 10-10.5. The solution is cooled to 5° C. and 3.73 g (0.022 mol) of benzylchloroformate is added dropwise while the pH is maintained at pH 10 with a 10% aqueous solution of sodium hydroxide. The mixture is stirred one hour, extracted with 100 ml of diethylether, the aqueous layer is separated and the pH is adjusted to pH 3-4 by the addition of a 10% aqueous solution of hydrochloric acid. The mixture is extracted with dichloromethane, 3×200 ml. The dichloromethane layer is separated, washed with a saturated aqueous solution of sodium chloride, 3×200 ml, separated, dried over sodium sulfate, evaporated and the residue is purified by chromatography using silica gel and eluting with dichloromethane-methanol (95:5) to give (S)-[[4-methyl2[[(phenylmethoxy)carbonyl]amino]pentyl]oxy]acetic acid, 5 g; [α]D25 -30.5 (c 0.55, methanol).

1. temperaturerefluxed for four hours
2. extractionextracted with 200 ml of dichloromethane
3. customThe aqueous layer is separated
4. customevaporated in vacuo
5. dissolutionthe residue dissolved in 200 ml of water
6. temperatureThe solution is cooled to 5° C.
7. extractionextracted with 100 ml of diethylether
8. customthe aqueous layer is separated
9. additionthe pH is adjusted to pH 3-4 by the addition of a 10% aqueous solution of hydrochloric acid
10. extractionThe mixture is extracted with dichloromethane, 3×200 ml
11. customThe dichloromethane layer is separated
12. washwashed with a saturated aqueous solution of sodium chloride, 3×200 ml
13. customseparated
14. dry with materialdried over sodium sulfate
15. customevaporated
16. customthe residue is purified by chromatography
17. washeluting with dichloromethane-methanol (95:5)