Dimethylformamide → Methyl 2-benzylisonicotinate

HRID 1963052Notes

Reaction equation

HRID 1963052 reaction equation
CN(C=O)C.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Cl[C:15]1[CH:20]=[C:19]([C:21]([O:23][CH3:24])=[O:22])[CH:18]=[CH:17][N:16]=1.[CH2:25](B1C2CCCC1CCC2)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.CC(=O)OCC>[CH2:25]([C:15]1[CH:20]=[C:19]([C:21]([O:23][CH3:24])=[O:22])[CH:18]=[CH:17][N:16]=1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 62657Potassium Phosphate, TribasicHCID 2736842Methyl 2-chloropyridine-4-carboxylateHCID 41509249-Benzyl-9-borabicyclo(3.3.1)nonane

Product 1

HCID 66731507Methyl 2-benzylisonicotinateYield 84.1%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To 35 ml of anhydrous DMF under argon in a sealed tube were added tripotassium phosphate (9.28 g, 43.71 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxy-biphenyl (SPhos, 0.239 g, 0.58 mmol), palladium(II) acetate (0.065 g, 0.29 mmol) and then methyl 2-chloro-pyridine-4-carboxylate (2.50 g, 14.57 mmol) and B-benzyl-9-borabicyclo[3.3.1]nonane (6.80 g, 32.05 mmol). The mixture was heated overnight at 60° C. After cooling to room temperature, the mixture was diluted into 200 ml of EA, the solution washed three times with 100 ml of a 1 N sodium hydroxide solution and twice with 100 ml of brine. The organic phase was dried over sodium sulfate, filtered and evaporated to dryness under reduced pressure. The residue was then purified by chromatography on silica gel (cyclohexane/EA, 100:0, then 80:20) to give 2.784 g of the title compound as an orange oil.

Workup

  1. temperatureAfter cooling to room temperature
  2. washthe solution washed three times with 100 ml of a 1 N sodium hydroxide solution
  3. dry with materialThe organic phase was dried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated to dryness under reduced pressure
  6. customThe residue was then purified by chromatography on silica gel (cyclohexane/EA, 100:0

Sources & evidence

ORD record
ord-2e9de2e192d841feaa493107aa8e9c82
Source dataset
uspto-grants-2013_04
Patent number
US08415336B2

Reaction notes

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