Potassium Carbonate → Methyl 5-[3-fluoro-4-(2,2,2-trifluoroethyl)phenyl]nicotinate

HRID 661247Notes

Reaction equation

HRID 661247 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([F:12])([F:11])[F:10])=[C:4]([F:13])[CH:3]=1.Cl.[CH3:15][O:16][C:17]([C:19]1[CH:20]=[C:21](B(O)O)[CH:22]=[N:23][CH:24]=1)=[O:18].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:13][C:4]1[CH:3]=[C:2]([C:21]2[CH:22]=[N:23][CH:24]=[C:19]([CH:20]=2)[C:17]([O:16][CH3:15])=[O:18])[CH:7]=[CH:6][C:5]=1[CH2:8][C:9]([F:12])([F:11])[F:10]

Participants

10

Reactant 4

HCID 11430Potassium CarbonateHCID 522689Potassium FluorideHCID 543109244-Bromo-2-fluoro-1-(2,2,2-trifluoroethyl)benzeneHCID 66890177[5-(Methoxycarbonyl)pyridin-3-yl]boronic acid hydrochloride

Product 1

HCID 58116533Methyl 5-[3-fluoro-4-(2,2,2-trifluoroethyl)phenyl]nicotinate

Reagents, catalysts & solvents 5

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

Procedure

A solution of 6.78 g (23.7 mmol, purity 90%) of the compound from Example 74A in toluene (339 ml) was admixed under argon at RT with 7.74 g (35.6 mmol) of the compound from Example 29A in ethanol (112 ml) and 3.61 g (26.1 mmol) of potassium carbonate. After stirring for 10 min, 2.74 g (2.37 mmol) of tetrakis(triphenylphosphine)palladium and then 4.14 g (71.2 mmol) of potassium fluoride in water (71 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, dichloromethane/methanol 150:1→100:1). The product fractions were concentrated under reduced pressure and the solid obtained was purified by stirring with diethyl ether. Yield: 6.00 g (50% of theory, purity 62%)

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, dichloromethane/methanol 150:1→100:1)
  9. concentrationThe product fractions were concentrated under reduced pressure
  10. customthe solid obtained
  11. customwas purified
  12. stirringby stirring with diethyl ether

Sources & evidence

ORD record
ord-0f85fc2012e24b76bfc6449bd39a0e12
Source dataset
uspto-grants-2011_12
Patent number
US08084469B2

Reaction notes

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