반응 #82372

반응 방정식

hydroxybenzotriazole

dicyclohexylcarbodiimide

N-(benzyloxycarbonyl)-3-cyano-L-alanine

N2 [3(S)-amino-2(R)-hydroxy-4-phenylbutyl]-N1 -tert.butyl-L-prolinamide

→

N2 [3(S)-[[N-(benzyloxycarbonyl)-3-cyano-L-alanyl]amino]-2(R)-hydroxy-4-phenylbutyl]-N1 -tert.butyl-L-prolinamide hemihydrate

수율 23.4%

용매

dimethyformamide

dichloromethane

반응 조건

후처리

1. 1
   온도cooled in an ice/salt bath
2. 2
   workup.STIRRINGThe mixture was stirred for 5 minutes
3. 3
   workup.STIRRINGwas then stirred overnight
4. 4
   여과The resulting dicyclohexylurea was filtered off
5. 5
   세척washed with methylene chloride
6. 6
   기타The combined filtrate and washings were evaporated at 40° C. in a vacuum
7. 7
   기타to give an oil which
8. 8
   기타was partitioned between ethyl acetate and water
9. 9
   세척The organic phase was washed in sequence with saturated aqueous sodium bicarbonate solution and saturated sodium chloride solution
10. 10
    건조dried over sodium sulphate
11. 11
    기타The solvent was removed by evaporation
12. 12
    기타to give an oil which
13. 13
    기타was chromatographed on silica gel using 14% methanol in dichloromethane for the elution
14. 14
    기타was recrystallized from diethyl ether/n-hexane

실험 절차

0.122 g of N-(benzyloxycarbonyl)-3-cyano-L-alanine was dissolved in 2 ml of dry dimethyformamide. The solution was stirred and cooled in an ice/salt bath and treated with 0.066 g of hydroxybenzotriazole and 0.1 g of dicyclohexylcarbodiimide. The mixture was stirred for 5 minutes and then treated with 0.163 g of N2 -[3(S)-amino-2(R)-hydroxy-4-phenylbutyl]-N1 -tert.butyl-L-prolinamide in 2.5 ml of dry dichloromethane. The mixture was allowed to warm to room temperature and was then stirred overnight. The resulting dicyclohexylurea was filtered off and washed with methylene chloride. The combined filtrate and washings were evaporated at 40° C. in a vacuum to give an oil which was partitioned between ethyl acetate and water. The organic phase was washed in sequence with saturated aqueous sodium bicarbonate solution and saturated sodium chloride solution and then dried over sodium sulphate. The solvent was removed by evaporation to give an oil which was chromatographed on silica gel using 14% methanol in dichloromethane for the elution. There were thus obtained 50 mg of product which was recrystallized from diethyl ether/n-hexane to give 0.045 g of N2 -[3(S)-[[N-(benzyloxycarbonyl)-3-cyano-L-alanyl]amino]-2(R)-hydroxy-4-phenylbutyl]-N1 -tert.butyl-L-prolinamide hemihydrate as a solid of melting point 65°-70° C. (softening).

출처