Oxygen → 1-[(2',6'-Difluoro-4'-methoxy-6-trifluoromethyl-biphenyl-3-carbonyl)-amino]-4-methyl-cyclohexanecarboxylic Acid Methyl Ester

HRID 1918362Notes

Reaction equation

HRID 1918362 reaction equation
[CH3:1][O:2][C:3]([C:5]1([NH:12][C:13](=[O:25])[C:14]2[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[C:16](Br)[CH:15]=2)[CH2:10][CH2:9][CH:8]([CH3:11])[CH2:7][CH2:6]1)=[O:4].[F:26][C:27]1[CH:32]=[C:31]([O:33][CH3:34])[CH:30]=[C:29]([F:35])[C:28]=1B(O)O.C1(P(C2CCCCC2)C2C=CC=CC=2OC2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O=O>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC(=O)OCC.C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]([C:5]1([NH:12][C:13]([C:14]2[CH:15]=[C:16]([C:28]3[C:27]([F:26])=[CH:32][C:31]([O:33][CH3:34])=[CH:30][C:29]=3[F:35])[C:17]([C:20]([F:23])([F:22])[F:21])=[CH:18][CH:19]=2)=[O:25])[CH2:10][CH2:9][CH:8]([CH3:11])[CH2:7][CH2:6]1)=[O:4]

Participants

9

Reactant 5

HCID 977OxygenHCID 62657Potassium Phosphate, TribasicHCID 4499096Bis(2-dicyclohexylphosphinophenyl)ether2×HCID 162174242,6-Difluoro-4-methoxybenzeneboronic acid2×HCID 671705141-(3-Bromo-4-trifluoromethyl-benzoylamino)-4-methyl-cyclohexanecarboxylic acid methyl ester

Product 1

HCID 671688001-[(2',6'-Difluoro-4'-methoxy-6-trifluoromethyl-biphenyl-3-carbonyl)-amino]-4-methyl-cyclohexanecarboxylic Acid Methyl EsterYield 4.6%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

300 mg of 1-(3-Bromo-4-trifluoromethyl-benzoylamino)-4-methyl-cyclohexanecarboxylic acid methyl ester, 267 mg of 2,6-difluoro-4-methoxyphenylboronic acid, 65 mg of tris(dibenzylideneacetone)di-palladium(0), 96 mg of bis(2-dicyclohexylphosphinophenyl)ether, 453 mg of K3PO4, and 1 g of molecular sieve 4 Å were added to 10 ml of toluene. The mixture was made oxygen-free by passing argon through it. Then, the mixture was kept at 160° C. under microwave irradiation for 2 h. Then, 267 mg of 2,6-difluoro-4-methoxyphenylboronic acid, 65 mg of tris(dibenzylideneacetone)di-palladium(0), 96 mg of bis(2-dicyclohexylphosphinophenyl)ether were added and the mixture was kept at 160° C. under microwave irradiation for 2 h. The mixture was cooled to room temperature and 100 ml of EA added. The mixture was then washed twice using 20 ml of a saturated aqueous Na2CO3-solution each. The organic layer was dried using MgSO4 and the solvent evaporated. Chromatography on silica gel using EA/HEP 1:5 yielded 16 mg of the title compound, viscous oil.

Workup

  1. customThen, the mixture was kept at 160° C. under microwave irradiation for 2 h
  2. customthe mixture was kept at 160° C. under microwave irradiation for 2 h
  3. washThe mixture was then washed twice
  4. customThe organic layer was dried
  5. customthe solvent evaporated

Sources & evidence

ORD record
ord-a8a6adb5cb1d48ae8808bd61fdfae16b
Source dataset
uspto-grants-2013_12
Patent number
US08618304B2

Reaction notes

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