Potassium Carbonate → Methyl 5-(4-(1,1-difluoroethyl)phenyl)nicotinate

HRID 661244Notes

Reaction equation

HRID 661244 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[CH3:9])=[CH:4][CH:3]=1.Cl.[CH3:13][O:14][C:15]([C:17]1[CH:18]=[C:19](B(O)O)[CH:20]=[N:21][CH:22]=1)=[O:16].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:8]([C:5]1[CH:6]=[CH:7][C:2]([C:19]2[CH:20]=[N:21][CH:22]=[C:17]([CH:18]=2)[C:15]([O:14][CH3:13])=[O:16])=[CH:3][CH:4]=1)([F:11])[CH3:9]

Participants

10

Reactant 4

HCID 11430Potassium CarbonateHCID 522689Potassium FluorideHCID 451588471-Bromo-4-(1,1-difluoroethyl)benzeneHCID 66890177[5-(Methoxycarbonyl)pyridin-3-yl]boronic acid hydrochloride

Product 1

HCID 58116582Methyl 5-(4-(1,1-difluoroethyl)phenyl)nicotinate

Reagents, catalysts & solvents 5

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

Procedure

A solution of 2.98 g (13.3 mmol) of the compound from Example 68A in toluene (25.0 ml) was admixed under argon at RT with 3.62 g (16.7 mmol) of the compound from Example 29A in ethanol (8.4 ml) and 2.03 g (14.7 mmol) of potassium carbonate. After stirring for 10 min, 1.54 g (1.34 mmol) of tetrakis(triphenylphosphine)palladium and then 2.33 g (40.0 mmol) of potassium fluoride in water (5.8 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: 2.62 g (69% of theory, 4:1 mixture of methyl and ethyl ester)

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)
  9. additionYield: 2.62 g (69% of theory, 4:1 mixture of methyl and ethyl ester)

Sources & evidence

ORD record
ord-a40fb95621dc4a9abb0abe87f4a2482c
Source dataset
uspto-grants-2011_12
Patent number
US08084469B2

Reaction notes

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