Thiazolidine → Pro-Ile

HRID 6616

反応式

HRID 6616 の反応式
[N:1]1(C(OC(C)(C)C)=O)[CH2:16][CH2:15][CH2:14][C@H:2]1[C:3]([NH:5][C@H:6]([C:11]([OH:13])=[O:12])[C@H:7]([CH2:9][CH3:10])[CH3:8])=[O:4].ON1C2C=CC=CC=2N=N1.S1CCNC1.C1(N=C=NC2CCCCC2)CCCCC1>ClCCl.C(OCC)(=O)C>[NH:1]1[CH2:16][CH2:15][CH2:14][C@H:2]1[C:3]([NH:5][C@H:6]([C:11]([OH:13])=[O:12])[C@H:7]([CH2:9][CH3:10])[CH3:8])=[O:4]

参加物

7

反応物 4

HCID 10444ThiazolidineHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 52951134Boc-Pro-Ile-OH

生成物 1

HCID 7079601Pro-Ile収率 80%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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.

後処理

  1. stirringStirring
  2. filtrationthe solution is thoroughly filtered off from the dicyclohexylurea that
  3. customis precipitated out
  4. customthe residue obtained
  5. washThe 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. dry with materialThe ethyl acetate phase is dried over Na2SO4
  7. concentrationconcentrated
  8. customa rotary evaporator
  9. customthe remaining crude product is recrystallised
  10. customBoc-Pro-Ile-Thia crystallises after 1–2 days at 4° C. (yield 80%)
  11. addition1.1N HC1/glacial acetic acid solution is added to Boc-Pro-Ile-Thia (3 ml per mmol of peptide)
  12. stirringStirring
  13. waitis carried out for two hours at RT
  14. additionabsolute ether is added
  15. customexcess removal solution is evaporated off
  16. customa rotary evaporator
  17. customThe hydrochloride crystallises quantitatively under absolute ether overnight at 4° C
  18. customThe crystals are quickly separated off by suction filtration
  19. washwashed several times with absolute ether
  20. customthe product is stored in a desiccator over KOH or phosphorus pentoxide

出典と根拠

ORDレコード
ord-6d6f150a18ea41f783d9bece53d51bab
出典データセット
uspto-grants-2006_08
特許番号
US07084120B2

関連ノート

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