Dimethylformamide → Diethyl 2-(2',3-dimethyl-2,4'-bipyridin-5-yl)malonate

HRID 592184Notes

Reaction equation

HRID 592184 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([CH:8]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:4][C:3]=1[CH3:19].[CH3:20][C:21]1[CH:26]=[C:25]([Sn](CCCC)(CCCC)CCCC)[CH:24]=[CH:23][N:22]=1.CN(C=O)C.[F-].[K+]>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>[CH3:20][C:21]1[CH:26]=[C:25]([C:2]2[C:3]([CH3:19])=[CH:4][C:5]([CH:8]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:6][N:7]=2)[CH:24]=[CH:23][N:22]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 522689Potassium FluorideHCID 216605742-Methyl-4-(tributylstannyl)pyridineHCID 58447937Diethyl 2-(6-chloro-5-methylpyridin-3-yl)malonate

Product 1

HCID 58447640Diethyl 2-(2',3-dimethyl-2,4'-bipyridin-5-yl)malonate

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To a reaction flask containing diethyl 2-(6-chloro-5-methylpyridin-3-yl)malonate 156-3 (1.00 g, 4.00 mmol), 2-methyl-4-(tributylstannyl)pyridine (1.53 g, 4.00 mmol) and Pd(PPh3)4 (440 mg, 0.4 mmol) under argon was added DMF (20 mL). The mixture was stirred at 120° C. for 10 hours. After the mixture was cooled down to room temperature, 1N KF aqueous solution was added to it and stirred for 15 minutes. The mixture was diluted with ethyl acetate and the two layers were separated. The organic layer was further washed with water and brine, dried over Na2SO4, concentrated to dryness by rotary evaporation. The crude product was purified by silica gel flash chromatography, eluted with 5% methanol in dichloromethane to give diethyl 2-(2′,3-dimethyl-2,4′-bipyridin-5-yl)malonate 156-4 as colorless oil. MS m/z 343.1 (M+1)

Workup

  1. temperatureAfter the mixture was cooled down to room temperature
  2. stirringstirred for 15 minutes
  3. customthe two layers were separated
  4. washThe organic layer was further washed with water and brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated to dryness by rotary evaporation
  7. customThe crude product was purified by silica gel flash chromatography
  8. washeluted with 5% methanol in dichloromethane

Sources & evidence

ORD record
ord-691b6da43a8b481bb483f63b36ecb242
Source dataset
uspto-grants-2016_01
Patent number
US09238646B2

Reaction notes

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