Cesium carbonate → 6-(4-Fluoro-3-(trifluoromethyl)phenyl)picolinaldehyde

HRID 1472923Notes

Reaction equation

HRID 1472923 reaction equation
Br[C:2]1[N:7]=[C:6]([CH:8]=[O:9])[CH:5]=[CH:4][CH:3]=1.[F:10][C:11]1[CH:16]=[CH:15][C:14](B(O)O)=[CH:13][C:12]=1[C:20]([F:23])([F:22])[F:21].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1>[F:10][C:11]1[CH:16]=[CH:15][C:14]([C:2]2[N:7]=[C:6]([CH:8]=[O:9])[CH:5]=[CH:4][CH:3]=2)=[CH:13][C:12]=1[C:20]([F:21])([F:22])[F:23]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 27570096-Bromopyridine-2-carbaldehydeHCID 177500514-Fluoro-3-(trifluoromethyl)benzeneboronic acid

Product 1

HCID 848199696-(4-Fluoro-3-(trifluoromethyl)phenyl)picolinaldehydeYield 91%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 6-bromopicolinaldehyde (1.00 g, 5.38 mmol) in dioxane (30 mL) at ambient temperature was added 4-fluoro-3-(trifluoromethyl)phenylboronic acid (1.11 g, 5.38 mmol), 2M cesium carbonate (8.0 mL, 16 mmol) and 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (0.220 g, 0.269 mmol). The mixture was degassed (3× vacuum/purge N2), then heated at 80° C. overnight. After cooling to room temperature the mixture was concentrated and the residue partitioned between water and CH2Cl2. The organic extract was concentrated and purified by chromatography (10% ethyl acetate:hexanes) to provide 1.31 g (91%) of the title compound. MS (DCI+) m/z 270 (M+H).

Workup

  1. customThe mixture was degassed
  2. custom(3× vacuum/purge N2)
  3. temperatureAfter cooling to room temperature the mixture
  4. concentrationwas concentrated
  5. customthe residue partitioned between water and CH2Cl2
  6. extractionThe organic extract
  7. concentrationwas concentrated
  8. custompurified by chromatography (10% ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-85a26152321e4d208c3397dbc1cb8f62
Source dataset
uspto-grants-2015_04
Patent number
US09012651B2

Reaction notes

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