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

HRID 1459885
Notes
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Reaction equation

HRID 1459885 reaction equation
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]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

10

Reactant 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, compound

Product 1

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

Reagents, catalysts & solvents 3

HCID 9942167Palladium hydroxideCatalystHCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-40b3d715bfe24a7f9d42f3942dc7781a
Source dataset
uspto-grants-1998_12
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US05854275

Reaction notes

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