Hydrochloric Acid → Enalapril

HRID 273895

反応式

HRID 273895 の反応式
[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].[CH2:14]([O:16][C:17](=[O:28])[C:18](=O)[CH2:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH3:15].Cl>C(O)C.[Ni]>[CH2:14]([O:16][C:17]([C@@H:18]([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])[CH2:19][CH2:20][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)=[O:28])[CH3:15]

参加物

6

反応物 3

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

生成物 1

HCID 5388962Enalapril

試薬・触媒・溶媒 2

HCID 935Nickel触媒HCID 702Ethanol溶媒2 回

実験手順

50 moles (9.3 g) Ala-Pro were suspended in 100 ml ethanol, combined with 75 moles (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: 76.7%, product yield (according to HPLC): 35%. The residue was taken up is 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 was adjusted, then the entire amount was calculated). The solution was evaporated to low bulk under reduced pressure at 40° C. to 50 g, filtered by Celite and diluted to 100 ml total volume with ethyl acetate. 5.2 g maleic acid dissolved in ethyl acetate+ethanol were added and seeded with enalapril maleate. The crystallizate formed was separated off and dried.

後処理

  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. custom76.7%, 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 by 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

出典と根拠

ORDレコード
ord-40f8e8ab87034f02abede62d3ed86dc5
出典データセット
uspto-grants-1995_02
特許番号
US05387696

関連ノート

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