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Triethylamine → 4-Hydroxy-2-{1-[2-(4-methoxyphenyl)-1-(methylcarbamoyl)ethylcarbamoyl]cyclohexylmethyl}butyric acid tert-butyl ester

HRID 1459885
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1459885
C([O:8][CH2:9][CH2:10][CH:11]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:12][C:13]1([C:19]([OH:21])=O)[CH2:18][CH2:17][CH2:16][CH:15]=[CH:14]1)C1C=CC=CC=1.Cl.C[NH-].[CH3:32][O:33][C:34]1[CH:45]=[CH:44][C:37]([CH2:38][C@@H:39]([C:41](O)=[O:42])[NH2:40])=[CH:36][CH:35]=1.O.O[N:48]1[C:52]2C=CC=CC=2N=N1.C(N(CC)CC)C.Cl.CN(C)CCCN=C=NCC.[H][H]>C(Cl)Cl.C(O)C.[OH-].[OH-].[Pd+2]>[C:25]([O:24][C:22](=[O:23])[CH:11]([CH2:12][C:13]1([C:19](=[O:21])[NH:40][CH:39]([C:41](=[O:42])[NH:48][CH3:52])[CH2:38][C:37]2[CH:44]=[CH:45][C:34]([O:33][CH3:32])=[CH:35][CH:36]=2)[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18]1)[CH2:10][CH2:9][OH:8])([CH3:26])([CH3:27])[CH3:28]
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Komponenten

10

Edukt 6

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 541070441-(4-Benzyloxy-2-tert-butoxycarbonylbutyl)cyclohex-2-ene carboxylic acidHCID 131721053L-tyrosine methyl ether N-methylamide hydrochloride
HCID 178418361
HCID 178418361, Verbindung

Produkt 1

HCID 867535004-Hydroxy-2-{1-[2-(4-methoxyphenyl)-1-(methylcarbamoyl)ethylcarbamoyl]cyclohexylmethyl}butyric acid tert-butyl ester

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9942167Palladium hydroxideKatalysatorHCID 702EthanolLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of 1-(4-benzyloxy-2-tert-butoxycarbonylbutyl) cyclohex-2-ene carboxylic acid (a mixture of the two diastereomers) (2.5 g, 6.43 mmol) in methylene chloride (100 mL) were added successively L-tyrosine methyl ether N-methylamide hydrochloride (1.7 g, 6.95 mmol), 1-hydroxybenztriazole hydrate (959 mg, 6.26 mmol), triethylamine (0.98, 7.03 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodimide hydrochloride (1.36 g, 7.09 mmol). The resulting mixture was stirred overnight at room temperature and, after dilution with methylene chloride, was washed with 0.5M HCl solution and brine. The solvent was removed by evaporation under reduced vacuum leaving an oil which was chromatographed on silica gel eluting with 50% ethyl acetate in hexane. Fractions enriched in the desired product (4-benzyloxy-2-{1-[2-(4-methoxy-phenyl)-1-(methylcarbamoyl)ethylcarbamoyl]cyclohex-2-enylmethyl}butyric acid tert-butyl ester) were combined and concentrated to leave an oil, 2.2 g. The oil was dissolved in ethanol (50 mL) to which was added 20% palladium hydroxide on carbon (500 mg). The mixture was agitated overnight in a Parr shaker under 3 atmospheres of hydrogen. After removal of the catalyst by filtration through diatomaceous earth, the solvent was evaporated to leave an oil from which 4-hydroxy-2-{1-[2-(4-methoxyphenyl)-1-(methylcarbamoyl)ethylcarbamoyl]cyclohexylmethyl}butyric acid tert-butyl ester, an oily 2:1 mixture of two diastereomers, 1.2 g (38%), was isolated by chromatography on silica gel eluting with 20% hexane in ethyl acetate.

Aufarbeitung

  1. washafter dilution with methylene chloride, was washed with 0.5M HCl solution and brine
  2. customThe solvent was removed by evaporation under reduced vacuum
  3. customleaving an oil which
  4. customwas chromatographed on silica gel eluting with 50% ethyl acetate in hexane
  5. concentrationconcentrated
  6. customto leave an oil, 2.2 g
  7. customAfter removal of the catalyst
  8. filtrationby filtration through diatomaceous earth
  9. customthe solvent was evaporated

Quellen und Nachweise

ORD-Eintrag
ord-40b3d715bfe24a7f9d42f3942dc7781a
Quelldatensatz
uspto-grants-1998_12
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US05854275

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