反应详情

A solution of ethyl 6-(1-benzyloxycarbonyl-4-piperidyl)-2-oxohexanoate [prepared according to Chem. Pharm. Bull, 34, 3747 (1986)] (7.4 g) and Nε -benzyloxycarbonyl-L-lysyl-L-proline benzylester.trifluoroacetic acid salt (4.6 g) in ethanol (40 ml) is adjusted to pH 5 with triethylamine. To this solution is added 2 g of molecular sieves, and the reaction mixture is stirred for 30 minutes. A solution of sodiumcyanoborohydride (1.4 g) in ethanol (40 ml) is dropped therein under stirring for 5 hours, and is kept stirring for further one night. The ethanol is distilled under reduced pressure, thereafter the residue is transferred to ethyl acetate. The ethyl acetate layer is washed with water, dried with anhydrous sodium sulfate, and concentrated under reduced pressure. To the residue ether is added. The ether layer is washed with water and then ether is distilled under reduced pressure. The residue is applied to silica gel chromatography (ethyl acetate:hexane=2:1) to obtain, from the first effluence, 1.34 g of Nα -[1(R)-ethoxycarbonyl- 5-(1-benzyloxycarbonyl-4-piperidyl)pentyl]-Nε -benzyloxycarbonyl-L-lysyl-L-proline benzylester (Rf=0.62, expansive solvent, F), and from the following effluence, 1.15 g of Nα -[1(S)ethoxycarbonyl-5-(1-benzyloxycarbonyl-4-piperidyl)pentyl]-Nε -benzyloxycarbonyl-L-proline benzylester (Rf=0.52, expansive solvent, F).

1. additionTo this solution is added 2 g of molecular sieves
2. stirringunder stirring for 5 hours
3. stirringis kept stirring for further one night
4. distillationThe ethanol is distilled under reduced pressure
5. washThe ethyl acetate layer is washed with water
6. dry with materialdried with anhydrous sodium sulfate
7. concentrationconcentrated under reduced pressure
8. additionTo the residue ether is added
9. washThe ether layer is washed with water
10. distillationether is distilled under reduced pressure