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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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HRID 1459885 반응식
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]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

10

반응물 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 hydrochlorideHCID 178418361HCID 178418361, 화합물

생성물 1

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

시약·촉매·용매 3

HCID 9942167Palladium hydroxide촉매HCID 702Ethanol용매HCID 6344Dichloromethane용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-40b3d715bfe24a7f9d42f3942dc7781a
출처 데이터셋
uspto-grants-1998_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US05854275

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