m-Toluidine → HCID 67221076, compound

HRID 1969070Notes

Reaction equation

HRID 1969070 reaction equation
[CH3:1][O:2][C:3](=[O:36])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][C:13]=2[CH2:22][N:23]([S:26]([C:29]2[CH:34]=[CH:33][C:32](Br)=[CH:31][CH:30]=2)(=[O:28])=[O:27])[CH2:24][CH3:25])[CH:6]=1.[NH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[C:40]([CH3:44])[CH:39]=1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.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]>[CH3:1][O:2][C:3](=[O:36])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][C:13]=2[CH2:22][N:23]([CH2:24][CH3:25])[S:26]([C:29]2[CH:34]=[CH:33][C:32]([NH:37][C:38]3[CH:39]=[C:40]([CH3:44])[CH:41]=[CH:42][CH:43]=3)=[CH:31][CH:30]=2)(=[O:28])=[O:27])[CH:6]=1

Participants

7

Reactant 4

HCID 7934m-ToluidineHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 58288537HCID 58288537, compound

Product 1

HCID 67221076HCID 67221076, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

[3-(2-{[(4-Bromo-benzenesulfonyl)-ethyl-amino]-methyl}-4-trifluoromethyl-phenoxy)-phenyl]-acetic acid methyl ester (0.183 g, 0.31 mmol), m-toluidine (0.04 mL, 0.38 mmol), and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.009 g, 0.02 mmol) were combined in 1,4-dioxane (3.6 mL). Cesium carbonate (0.505 g, 1.55 mmol) and tris(dibenzylideneacetone)dipalladium (0) (0.028 g, 0.03 mmol) were added, and the mixture was purged with N2 for 15 minutes and then stirred at 70° C. overnight under N2. Once no starting material was seen by analytical LCMS, the mixture was filtered through Celite. The filter cake was washed with EtOAc, and the filtrate was concentrated and purified by silica gel chromatography (10-30% EtOAc in hexanes) to give the title compound.

Workup

  1. customthe mixture was purged with N2 for 15 minutes
  2. filtrationthe mixture was filtered through Celite
  3. washThe filter cake was washed with EtOAc
  4. concentrationthe filtrate was concentrated
  5. custompurified by silica gel chromatography (10-30% EtOAc in hexanes)

Sources & evidence

ORD record
ord-e902a1a0d25b4f839408723af36b38c4
Source dataset
uspto-grants-2013_04
Patent number
US08426449B2

Reaction notes

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