Sodium Carbonate → 6-fluoro-1'-methyl-[3,4'-bipyridin]-2'(1'H)-one

HRID 595913Notes

Reaction equation

HRID 595913 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5](B2OC(C)(C)C(C)(C)O2)=[CH:4][N:3]=1.Br[C:18]1[CH:23]=[CH:22][N:21]([CH3:24])[C:20](=[O:25])[CH:19]=1.C([O-])([O-])=O.[Na+].[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].COCCOC>[F:1][C:2]1[N:3]=[CH:4][C:5]([C:18]2[CH:23]=[CH:22][N:21]([CH3:24])[C:20](=[O:25])[CH:19]=2)=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 121772222-Fluoropyridine-5-boronic acid pinacol esterHCID 221323964-Bromo-1-methylpyridin-2(1H)-one

Product 1

HCID 1180465486-fluoro-1'-methyl-[3,4'-bipyridin]-2'(1'H)-one

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (500 mg, 2.242 mmol) was added PdCl2(dppf) (68.3 mg, 0.093 mmol), 4-bromo-1-methylpyridin-2(1H)-one (351 mg, 1.868 mmol), 2M Na2CO3 (4.1 mL) and DME (8.3 mL) at room temperature. The reaction mixture was heated at microwave synthesizer for 10 min at 120° C. The reaction mixture was extracted with EtOAc. The organic layers were washed with water and brine, dried over anhydrous Na2SO4, filtered off, and concentrated in vacuo. The crude 6-fluoro-1′-methyl-[3,4′-bipyridin]-2′(1′H)-one was purified by flash chromatography (gradient EtOAc in DCM). LCMS (m/z): 205.2 (MH+), 0.47 min.

Workup

  1. extractionThe reaction mixture was extracted with EtOAc
  2. washThe organic layers were washed with water and brine
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered off
  5. concentrationconcentrated in vacuo
  6. customThe crude 6-fluoro-1′-methyl-[3,4′-bipyridin]-2′(1′H)-one was purified by flash chromatography (gradient EtOAc in DCM)
  7. custom205.2 (MH+), 0.47 min.

Sources & evidence

ORD record
ord-086f88ad15cf4748a40b4eb22b45651c
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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