Réaction #6712

Équation de réaction

dicyclohexylcarbodiimide

Boc-Pro-Ile-OH

N-hydroxybenzotriazole

thiazolidine

→

H-Pro-Ile

Rendement 80.0%

Solvants

ethyl acetate

dichloromethane

Conditions de réaction

Traitement

1. 1
   workup.STIRRINGStirring
2. 2
   Filtrationthe solution is thoroughly filtered off from the dicyclohexylurea that
3. 3
   Autreis precipitated out
4. 4
   Autrethe residue obtained
5. 5
   LavageThe ethyl acetate solution is washed at least three times with saturated bicarbonate solution, once with saturated NaC1 solution, three times with dilute KHSO4 solution and again with NaC1 solution
6. 6
   SéchageThe ethyl acetate phase is dried over Na2SO4
7. 7
   Concentrationconcentrated
8. 8
   Autrea rotary evaporator
9. 9
   Autrethe remaining crude product is recrystallised
10. 10
    AutreBoc-Pro-Ile-Thia crystallises after 1–2 days at 4° C. (yield 80%)
11. 11
    workup.ADDITION1.1N HC1/glacial acetic acid solution is added to Boc-Pro-Ile-Thia (3 ml per mmol of peptide)
12. 12
    workup.STIRRINGStirring
13. 13
    workup.WAITis carried out for two hours at RT
14. 14
    workup.ADDITIONabsolute ether is added
15. 15
    Autreexcess removal solution is evaporated off
16. 16
    Autrea rotary evaporator
17. 17
    AutreThe hydrochloride crystallises quantitatively under absolute ether overnight at 4° C
18. 18
    AutreThe crystals are quickly separated off by suction filtration
19. 19
    Lavagewashed several times with absolute ether
20. 20
    Autrethe product is stored in a desiccator over KOH or phosphorus pentoxide

Mode opératoire

6.5 mM Boc-Pro-Ile-OH (one equivalent=1 eq.) is suspended, together with N-hydroxybenzotriazole (1 eq.) and thiazolidine (1 eq.), in 30 ml of dichloromethane (DCM). The equivalent amount of 1M dicyclohexylcarbodiimide solution is added dropwise, at −10° C., with stirring. Stirring is carried out at −10° C. and overnight at room temperature. For the purpose of working-up, the solution is thoroughly filtered off from the dicyclohexylurea that is precipitated out, DCM is drawn off in vacuo and the residue obtained is taken up in ethyl acetate. The ethyl acetate solution is washed at least three times with saturated bicarbonate solution, once with saturated NaC1 solution, three times with dilute KHSO4 solution and again with NaC1 solution. The ethyl acetate phase is dried over Na2SO4 and concentrated using a rotary evaporator, and the remaining crude product is recrystallised using ethyl acetate/pentane. Boc-Pro-Ile-Thia crystallises after 1–2 days at 4° C. (yield 80%). 1.1N HC1/glacial acetic acid solution is added to Boc-Pro-Ile-Thia (3 ml per mmol of peptide). Stirring is carried out for two hours at RT, absolute ether is added and excess removal solution is evaporated off using a rotary evaporator. The hydrochloride crystallises quantitatively under absolute ether overnight at 4° C. The crystals are quickly separated off by suction filtration, washed several times with absolute ether, and the product is stored in a desiccator over KOH or phosphorus pentoxide.

Source