反应 #82372

反应方程式

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

收率 23.4%

溶剂

dimethyformamide

dichloromethane

反应条件

后处理

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

实验过程

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).

来源