Potassium Carbonate → 5-Cyclohex-1-enyl-6-(2,2,2-trifluoroethoxy)nicotinic acid methylester

HRID 240696

Reaction equation

HRID 240696 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[N:7][C:8]([O:12][CH2:13][C:14]([F:17])([F:16])[F:15])=[C:9](Br)[CH:10]=1)=[O:4].C(=O)([O-])[O-].[K+].[K+].[C:24]1(B2OC(C)(C)C(C)(C)O2)[CH2:29][CH2:28][CH2:27][CH2:26][CH:25]=1>CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[N:7][C:8]([O:12][CH2:13][C:14]([F:17])([F:16])[F:15])=[C:9]([C:24]2[CH2:29][CH2:28][CH2:27][CH2:26][CH:25]=2)[CH:10]=1)=[O:4]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 109326752-(Cyclohex-1-en-1-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 66686828Methyl 5-bromo-6-(2,2,2-trifluoroethoxy)nicotinate

Product 1

HCID 712944455-Cyclohex-1-enyl-6-(2,2,2-trifluoroethoxy)nicotinic acid methylesterYield 85.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

5-Bromo-6-(2,2,2-trifluoroethoxy)-3-pyridinecarboxylic acid methyl ester (500 mg, 1.59 mmol, CAN 1211589-51-3), potassium carbonate (660 mg, 4.78 mmol) and 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (65.0 mg, 79.6 μmol) were combined to give a light red solid. To this solid was added a solution of 2-(1-cyclohexen-1-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (331 mg, 1.59 mmol, CAN 141091-37-4) in DMF (12.0 ml), that had been thoroughly degassed and flushed with argon. The reaction mixture was heated to 80° C. and stirred for 48 h. Subsequently the reaction mixture was cooled to ambient temperature and poured into 75 mL brine and extracted with isopropyl acetate (2×150 mL). The organic layers were washed with brine (2×50 mL), combined and dried with Na2SO4 and concentrated in vacuo. The residue was purified by flash chromatography (silica gel, 50 g, 0% to 10%, n-heptane/isopropyl acetate) to give the title compound (0.43 g, 60%) as white solid; MS (EI) 316.3 (M+H)+.

Workup

  1. customto give a light red solid
  2. customhad been thoroughly degassed
  3. customflushed with argon
  4. temperatureSubsequently the reaction mixture was cooled to ambient temperature
  5. additionpoured into 75 mL brine
  6. extractionextracted with isopropyl acetate (2×150 mL)
  7. washThe organic layers were washed with brine (2×50 mL)
  8. dry with materialdried with Na2SO4
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by flash chromatography (silica gel, 50 g, 0% to 10%, n-heptane/isopropyl acetate)

Sources & evidence

ORD record
ord-71407f74e6494b1bbf8e5861566140cf
Source dataset
uspto-grants-2014_02
Patent number
US08648099B2

Linked notes

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