Potassium Fluoride → {4-[3-(4-Bromo-phenyl)-3-(3'-trifluoromethyl-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic Acid

HRID 2234146Notes

Reaction equation

HRID 2234146 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:24]2[CH:29]=[CH:28][C:27]([Br:30])=[CH:26][CH:25]=2)=[CH:9][CH2:10][S:11][C:12]2[CH:22]=[CH:21][C:15]([O:16][CH2:17][C:18]([OH:20])=[O:19])=[C:14]([CH3:23])[CH:13]=2)=[CH:4][CH:3]=1.[F:31][C:32]([F:43])([F:42])[C:33]1[CH:34]=[C:35](B(O)O)[CH:36]=[CH:37][CH:38]=1.[F-].[K+]>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(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[Br:30][C:27]1[CH:26]=[CH:25][C:24]([C:8]([C:5]2[CH:6]=[CH:7][C:2]([C:35]3[CH:36]=[CH:37][CH:38]=[C:33]([C:32]([F:43])([F:42])[F:31])[CH:34]=3)=[CH:3][CH:4]=2)=[CH:9][CH2:10][S:11][C:12]2[CH:22]=[CH:21][C:15]([O:16][CH2:17][C:18]([OH:20])=[O:19])=[C:14]([CH3:23])[CH:13]=2)=[CH:29][CH:28]=1

Participants

6

Reactant 3

HCID 522689Potassium FluorideHCID 27343883-(Trifluoromethyl)phenylboronic acidHCID 10370262{4-[3,3-Bis-(4-bromo-phenyl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid

Product 1

HCID 66758886{4-[3-(4-Bromo-phenyl)-3-(3'-trifluoromethyl-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic Acid

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 178418851HCID 178418851, compoundCatalyst

Conditions

Temperature
50 °C

Procedure

A mixture of {4-[3,3-bis-(4-bromo-phenyl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid (described above) (231 mg, 0.421 mmol), 3-(trifluoromethyl)phenylboronic acid (203 mg, 1.07 mmol), KF (81 mg, 1.39 mmol), Pd2(dba)3 (23 mg, 0.025 mmol) and Pd(P(t-Bu)3)2 (26 mg, 0,051 mmol) was evacuated for air and kept under nitrogen. THF (5 ml) was added and the reaction mixture was stirred at 50° C. overnight. A saturated aqueous NH4Cl (5 ml) solution was added, and the mixture was extracted with methylene chloride (2×20 ml). The combined organic phases were dried an evaporated. The isolated products were further purified on HPLC using acetonitril:water (4:6) increasing to pure acetonitril as eluent. The title product was isolated as an E/Z mixture in 95 mg (37%) yield.

Workup

  1. customwas evacuated for air
  2. additionTHF (5 ml) was added
  3. additionA saturated aqueous NH4Cl (5 ml) solution was added
  4. extractionthe mixture was extracted with methylene chloride (2×20 ml)
  5. customThe combined organic phases were dried an evaporated
  6. customThe isolated products were further purified on HPLC
  7. temperatureincreasing to pure acetonitril as eluent

Sources & evidence

ORD record
ord-d982bae947c642fea801b1ce0f06dac8
Source dataset
uspto-grants-2010_05
Patent number
US07709528B2

Reaction notes

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