Реакция #95985

Уравнение реакции

N-methyl-morpholine

chloroformic acid isobutyl ester

agmatine-dichlorohydrate

triethylamine

benzyloxycarbonyl-D-phenylalanyl-L-proline

→

Benzyloxycarbonyl-D-phenylalanyl-L-prolyl-agmatine-chlorohydrate

Растворители

water

dimethylformamide

dimethylformamide

Условия реакции

Обработка

1. 1
   workup.ADDITIONare added
2. 2
   workup.ADDITIONwhen the following solution is poured into it
3. 3
   Температураcooled to -15° C
4. 4
   workup.STIRRINGThe reaction mixture is stirred for 2 hours at -15° C., for 1 hour
5. 5
   Температураwithout cooling
6. 6
   Другоеis evaporated at reduced pressure
7. 7
   workup.DISSOLUTIONThe evaporation residue is dissolved in 100 ml of 0.2 N hydrochloric acid
8. 8
   Экстракцияextracted three times with 20 ml of ethyl acetate
9. 9
   Экстракцияextracted five times with 20 ml of chloroform
10. 10
    ПромывкаThe combined chloroform layers are washed twice with 10 ml of water
11. 11
    Другоеevaporated at reduced pressure
12. 12
    Фильтрацияfiltered
13. 13
    Промывкаwashed with diethyl ether
14. 14
    Другоеair-dried

Методика

4 g (10 mmoles) of benzyloxycarbonyl-D-phenylalanyl-L-proline (Nikolaides et al.: J.Med.Chem., 11, 74, 1968) are dissolved in 20 ml of dimethylformamide, cooled to -15° C., and at this temperature and constant stirring 1.11 ml (10 mmoles) of N-methyl-morpholine and 1.32 ml (10 mmoles) of chloroformic acid isobutyl ester are added. Stirring is continued for 10 minutes when the following solution is poured into it: 2.05 g (10 mmoles) of agmatine-dichlorohydrate (in formula II A means an H2N--C(NH)-- residue, B a chlorine atom and n=2) are suspended in 15 ml of dimethylformamide, 2 ml of water, then 1.4 ml (10 mmoles) of triethylamine are added, and cooled to -15° C. The reaction mixture is stirred for 2 hours at -15° C., for 1 hour without cooling, then is evaporated at reduced pressure. The evaporation residue is dissolved in 100 ml of 0.2 N hydrochloric acid and extracted three times with 20 ml of ethyl acetate. The pH of the aqueous layer is adjusted with solid sodium hydrogen carbonate to 8.0 to 8.5, and extracted five times with 20 ml of chloroform. The combined chloroform layers are washed twice with 10 ml of water, and evaporated at reduced pressure. The residue is worked up with diethyl ether, filtered, washed with diethyl ether and air-dried. Yield: 4.1 g (75 percent) of the named compound. RF3 0.5 to 0.6.

Источник