反应详情

Under atmosphere of argon, to a solution of (2S)-2-(t-butoxycarbonylamino)-4-methylpentanoic acid (t-butoxycarbonyl-L-leucine) (37.4 g) in tetrahydrofuran (800 ml) was added N-methylmorpholine (33 ml) at −25° C. and the mixture was stirred for 10 minutes. To the mixture was added chloroethylformate (15.8 ml) and the mixture was stirred for 20 minutes. Thereto was added a solution of diazomethane in diethyl ether and the mixture was stirred for another 2 hours. Thereto was added a mixture of 47% hydrobromic acid-acetic acid (1:1) at 0° C. and the mixture was stirred for 15 minutes. To the reaction mixture was added water and was extracted with a mixture of ethyl acetate-hexane. The organic layer was washed with a saturated aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride successively, dried over anhydrous sodium sulfate and was concentrated. The residue was washed with cooled hexane to give the title compound (27.4 g) having the following physical data.

1. stirringthe mixture was stirred for 20 minutes
2. stirringthe mixture was stirred for another 2 hours
3. additionThereto was added
4. stirringthe mixture was stirred for 15 minutes
5. extractionwas extracted with a mixture of ethyl acetate-hexane
6. washThe organic layer was washed with a saturated aqueous solution of sodium bicarbonate
7. dry with materiala saturated aqueous solution of sodium chloride successively, dried over anhydrous sodium sulfate
8. concentrationwas concentrated
9. washThe residue was washed with cooled hexane