Hydrochloric Acid → Enalapril

HRID 273894

반응식

HRID 273894 반응식
[NH2:1][C@H:2]([C:4]([N:6]1[CH2:13][CH2:12][CH2:11][C@H:7]1[C:8]([OH:10])=[O:9])=[O:5])[CH3:3].C(N(CC)CC)C.[CH2:21]([O:23][C:24](=[O:35])[C:25](=O)[CH2:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH3:22].Cl>C(O)C.[Ni]>[CH2:21]([O:23][C:24]([C@@H:25]([NH:1][C@H:2]([C:4]([N:6]1[CH2:13][CH2:12][CH2:11][C@H:7]1[C:8]([OH:10])=[O:9])=[O:5])[CH3:3])[CH2:26][CH2:27][C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1)=[O:35])[CH3:22]

참가 물질

7

반응물 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 83525L-Alanyl-L-prolineHCID 562087Ethyl alpha-oxobenzenebutanoate

생성물 1

HCID 5388962Enalapril

시약·촉매·용매 2

HCID 935Nickel촉매HCID 702Ethanol용매2회

실험 절차

50 mmoles (9.3 g) Ala-Pro were suspended in 100 ml ethanol, mixed with 10 moles (1 g) triethylamine, 75 mmoles (15.5 g) 2-oxo-4-phenyl-butyric acid ethyl ester and 18 g molecular sieve 3 A and agitated for 2 hours under anhydrous conditions. One teaspoon of dehydrated Raney nickel and 15 g molecular sieve 3 A were now added, briefly reacted and subsequently hydrogenated for 22 hours under an atmosphere of 4 bars of H2. The reaction mixture was filtered and evaporated to concentrate it to a small volume. Conversion (according to HPLC) relative to Ala-Pro used: 95.6%, product yield (according to HPLC): 95%. The residue was taken up in 250 ml ethanol and adjusted to pH 4.25 with conc. HCl (an aliquot was removed for this purpose, diluted with water and the pH adjusted, then the entire amount of HCl required was calculated). The solution was evaporated to low bulk under reduced pressure at 40° C. to 50 g, filtered with Celite and diluted to 100 ml total volume with ethyl acetate. 5.2 g maleic acid dissolved in ethyl acetate+ethanol were added and the mixture was seeded with enalapril maleate. The crystallizate formed was separated off and dried.

후처리

  1. custombriefly reacted
  2. waitsubsequently hydrogenated for 22 hours under an atmosphere of 4 bars of H2
  3. filtrationThe reaction mixture was filtered
  4. customevaporated
  5. concentrationto concentrate it to a small volume
  6. custom95.6%, product yield (according to HPLC)
  7. customwas removed for this purpose
  8. additiondiluted with water
  9. customThe solution was evaporated to low bulk under reduced pressure at 40° C. to 50 g
  10. filtrationfiltered with Celite
  11. additiondiluted to 100 ml total volume with ethyl acetate
  12. dissolution5.2 g maleic acid dissolved in ethyl acetate+ethanol
  13. additionwere added
  14. customThe crystallizate formed
  15. customwas separated off
  16. customdried

출처 및 근거

ORD 기록
ord-b4e9e23721fc44e5b6ebfbf912418b5c
출처 데이터셋
uspto-grants-1995_02
특허 번호
US05387696

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