Hydrochloric Acid → Z-(L)-Pro-(L)-Ala-(L)-PhgOMe

HRID 1720012노트

반응식

HRID 1720012 반응식
[N:1]1([C:14]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:15])[CH2:13][CH2:12][CH2:11][C@H:2]1[C:3]([NH:5][C@H:6]([C:8]([OH:10])=O)[CH3:7])=[O:4].ON1C2C=CC=CC=2N=N1.CN(CCCN=C=NCC)C.Cl.[NH2:46][C@H:47]([C:54]([O:56][CH3:57])=[O:55])[C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1.Cl.CN1CCOCC1>C(Cl)Cl>[N:1]1([C:14]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:15])[CH2:13][CH2:12][CH2:11][C@H:2]1[C:3]([NH:5][C@H:6]([C:8]([NH:46][C@H:47]([C:54]([O:56][CH3:57])=[O:55])[C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)=[O:10])[CH3:7])=[O:4]

참가 물질

8

반응물 6

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 73513N-Benzyloxycarbonyl-L-prolyl-L-alanineHCID 757711-HydroxybenzotriazoleHCID 11217910(S)-(+)-2-Phenylglycine methyl ester hydrochloride

생성물 1

HCID 131719359Z-(L)-Pro-(L)-Ala-(L)-PhgOMe

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

A suspension of 1,500 g (4.68 mmoles) of Z-(L)-Pro-(L)-AlaOH (Sigma) in 60 ml of dry methylene chloride (CH2Cl2) was brought, under stirring and in an argon atmosphere, to the temperature of the ice and salt bath. The following were then added in succession: 0.800 g (4.73 mmoles) of commercial 1-hydroxybenzotriazole (HOBt) and 0.900 g (4.69 mmoles) of N-(dimethylaminopropyl)-N'-ethylcarbodiimide.HCl (EDC). Keeping the temperature under control, the mixture was left under stirring for 10 minutes and then the following were added in succession: 0.940 g (4.66 mmoles) of (L)-PhgOMe.HCl (Bachem) and 0.520 ml (4.72 mmoles) of 4-methylmorpholine (NMM), maintaining the temperature for a further 2 hours. The mixture was then left under stirring and static argon for 12 hours with the temperature free to rise to room temperature. The solid white precipitate was filtered away and washed with a little CH2Cl2. The latter was put back into the filtered reaction solution, which was extracted in succession using 5% NaHCO3 (3×30 ml); saturated aqueous NaCl (2×30 ml); 4% KHSO4 (3×30 ml) and finally saturated aqueous NaCl (2 ×30 ml), discarding the aqueous phases. The organic phase extracted was left in a cold chamber under argon and on anhydrous Na2SO4 for 12 hours. The desiccant was then filtered away, the solution concentrated to a small volume and the dense residual liquid was ground with anhydrous ethyl ether a number of times, decanting each time and discarding the ether phase. The residual solid was left for 24 hours under vacuum on P2O5. 1.630 g (74.8%) of an analytically pure powdery white solid were recovered.

후처리

  1. additionThe following were then added in succession
  2. waitthe mixture was left
  3. additionthe following were added in succession
  4. waitThe mixture was then left
  5. stirringunder stirring
  6. waitstatic argon for 12 hours with the temperature free to rise to room temperature
  7. filtrationThe solid white precipitate was filtered away
  8. washwashed with a little CH2Cl2
  9. customThe latter was put back into the filtered reaction solution, which
  10. extractionwas extracted in succession
  11. extractionThe organic phase extracted
  12. waitwas left in a cold chamber under argon and on anhydrous Na2SO4 for 12 hours
  13. filtrationThe desiccant was then filtered away
  14. concentrationthe solution concentrated to a small volume
  15. customdecanting each time
  16. waitThe residual solid was left for 24 hours under vacuum on P2O5
  17. custom1.630 g (74.8%) of an analytically pure powdery white solid were recovered

출처 및 근거

ORD 기록
ord-1fad6be3409949e09b46359801ab9baa
출처 데이터셋
uspto-grants-1996_04
특허 번호
US05504071

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