تفاعل #82372

معادلة التفاعل

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

المردود 23.4%

المذيبات

dimethyformamide

dichloromethane

ظروف التفاعل

المعالجة

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

الإجراء التجريبي

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).

المصدر