Potassium Carbonate → Methyl 5-[4-(2,2,2-trifluoroethyl)phenyl]nicotinate

HRID 661231Notes

Reaction equation

HRID 661231 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([F:12])([F:11])[F:10])=[CH:4][CH:3]=1.Cl.[CH3:14][O:15][C:16]([C:18]1[CH:19]=[C:20](B(O)O)[CH:21]=[N:22][CH:23]=1)=[O:17].C(=O)([O-])[O-].[K+].[K+].[F-].[K+]>C1(C)C=CC=CC=1.C(O)C.O.C(OCC)(=O)C.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>[F:10][C:9]([F:12])([F:11])[CH2:8][C:5]1[CH:6]=[CH:7][C:2]([C:20]2[CH:21]=[N:22][CH:23]=[C:18]([CH:19]=2)[C:16]([O:15][CH3:14])=[O:17])=[CH:3][CH:4]=1

Participants

10

Reactant 4

HCID 11430Potassium CarbonateHCID 522689Potassium FluorideHCID 100829441-Bromo-4-(2,2,2-trifluoroethyl)benzeneHCID 66890177[5-(Methoxycarbonyl)pyridin-3-yl]boronic acid hydrochloride

Product 1

HCID 58116526Methyl 5-[4-(2,2,2-trifluoroethyl)phenyl]nicotinate

Reagents, catalysts & solvents 5

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 8.00 g (33.5 mmol) of the compound from Example 51A in toluene (304 ml) was admixed under argon at RT with 10.9 g (50.2 mmol) of the compound from Example 29A in ethanol (100 ml) and 5.10 g (36.8 mmol) of potassium carbonate. After stirring for 10 min, 3.87 g (3.35 mmol) of tetrakis(triphenylphosphine)palladium and then 5.83 g (100 mmol) of potassium fluoride in water (64 ml) were added. The mixture was stirred under reflux for 8 h, and the reaction solution was cooled and diluted with ethyl acetate. The reaction solution was washed in water, and the organic phase was dried over magnesium sulphate, filtered and concentrated under reduced pressure. The residue was purified by means of column chromatography (silica gel, dichloromethane/methanol 100:1→80:1). Yield: 9.20 g (69% of theory, purity 75%)

Workup

  1. stirringThe mixture was stirred
  2. temperatureunder reflux for 8 h
  3. temperaturethe reaction solution was cooled
  4. washThe reaction solution was washed in water
  5. dry with materialthe organic phase was dried over magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by means of column chromatography (silica gel, dichloromethane/methanol 100:1→80:1)

Sources & evidence

ORD record
ord-f4a2dc3714a44bd7800b23e5647e8f01
Source dataset
uspto-grants-2011_12
Patent number
US08084469B2

Reaction notes

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