Ethanol → 2-Chloro-2'-(phenylmethoxy)-5'-(trifluoromethyl)-[1,1'-biphenyl]-4-amine

HRID 1694733Notes

Reaction equation

HRID 1694733 reaction equation
[C:1]1([CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][C:10]=2B(O)O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[C:23]1[CH:29]=[CH:28][C:26]([NH2:27])=[CH:25][C:24]=1[Cl:30].C(O)C.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:30][C:24]1[CH:25]=[C:26]([NH2:27])[CH:28]=[CH:29][C:23]=1[C:10]1[CH:11]=[C:12]([C:15]([F:18])([F:17])[F:16])[CH:13]=[CH:14][C:9]=1[O:8][CH2:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

7

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 888884-Bromo-3-chloroanilineHCID 230053392-Benzyloxy-5-trifluoromethylphenylboronic acid

Product 1

HCID 672800212-Chloro-2'-(phenylmethoxy)-5'-(trifluoromethyl)-[1,1'-biphenyl]-4-amine

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Procedure

The product from example 32 step (ii) (0.5 g) and 4-bromo-3-chloroaniline (0.38 g) were dissolved in toluene (4 ml). Ethanol (1 ml), 2M aqueous sodium carbonate (1 ml) and Pd(PPh3)4 (0.115 g) were added sequentially and the mixture heated at reflux for 4 h. The reaction was cooled, evaporated, dissolved in EtOAc, washed with water and brine, dried (MgSO4) and evaporated. The residue was purified by chromatography on silica eluting with 10% EtOAc/isohexane. Yield 0.23 g.

Workup

  1. temperaturethe mixture heated
  2. temperatureat reflux for 4 h
  3. temperatureThe reaction was cooled
  4. customevaporated
  5. dissolutiondissolved in EtOAc
  6. washwashed with water and brine
  7. dry with materialdried (MgSO4)
  8. customevaporated
  9. customThe residue was purified by chromatography on silica eluting with 10% EtOAc/isohexane

Sources & evidence

ORD record
ord-fe5492cad9d14d0f97a838d8f1807c9c
Source dataset
uspto-grants-2012_04
Patent number
US08158820B2

Reaction notes

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