Cesium carbonate → Methyl 2-(4-fluorophenyl)pyridine-4-carboxylate

HRID 602381Notes

Reaction equation

HRID 602381 reaction equation
Cl[C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6].C(=O)([O-])[O-].[Cs+].[Cs+].[F:18][C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][CH:20]=1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:18][C:19]1[CH:24]=[CH:23][C:22]([C:2]2[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=2)[C:5]([O:7][CH3:8])=[O:6])=[CH:21][CH:20]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 2856454-Fluorophenylboronic acidHCID 2736842Methyl 2-chloropyridine-4-carboxylate

Product 1

HCID 66732391Methyl 2-(4-fluorophenyl)pyridine-4-carboxylateYield 70.2%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

Methyl 2-chloroisonicotinate (300 mg, 1.75 mmol) obtained in Step 1 of Reference Example 5 was dissolved in toluene (3.5 mL), and the solution was added with palladium acetate (11.8 mg, 0.0525 mmol), 2,2′-bis(diphenylphosphino)-2,2′-binaphthyl (49.1 mg, 0.0788 mmol), cesium carbonate (798 mg, 2.45 mmol) and 4-fluorophenylboronic acid (294 mg, 2.10 mmol), followed by stirring at 100° C. for 1 hour under argon atmosphere. After an insoluble matter of the reaction mixture was filtered off, the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane=5/95 to 10/90) to obtain Methyl 2-(4-fluorophenyl)isonicotinate (284 mg, 70%).

Workup

  1. filtrationAfter an insoluble matter of the reaction mixture was filtered off
  2. customthe solvent was evaporated under reduced pressure
  3. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane=5/95 to 10/90)

Sources & evidence

ORD record
ord-6f114db8d62847949ad91b8300423e0b
Source dataset
uspto-grants-2011_03
Patent number
US07906522B2

Reaction notes

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