Sodium Carbonate → 2-Fluoro-3-(2-methylpyridin-4-yl)pyridine

HRID 410179

Reaction equation

HRID 410179 reaction equation
Br[C:2]1[C:3]([F:8])=[N:4][CH:5]=[CH:6][CH:7]=1.[CH3:9][C:10]1[CH:15]=[C:14](B(O)O)[CH:13]=[CH:12][N:11]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd]>[F:8][C:3]1[C:2]([C:14]2[CH:13]=[CH:12][N:11]=[C:10]([CH3:9])[CH:15]=2)=[CH:7][CH:6]=[CH:5][N:4]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 27627783-Bromo-2-fluoropyridineHCID 41926642-Methylpyridine-4-boronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl

Product 1

HCID 585485722-Fluoro-3-(2-methylpyridin-4-yl)pyridine

Reagents, catalysts & solvents 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

To a round bottomed flask was added 3-bromo-2-fluoropyridine (1.0376 g, 5.9 mmol), 2-methylpyridin-4-ylboronic acid (1.6154 g, 12 mmol), tris(dibenzylideneacetone)dipalladium(o) (0.5501 g, 0.59 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (0.4846 g, 1.2 mmol), and sodium carbonate (0.74 mL, 18 mmol) in acetonitrile:water (5:1 ratio) at 85° C. to stir overnight. The reaction was monitored by LCMS. Upon completion, the solvents were evaporated. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Biotage™ pre-packed silica gel column (40S), eluting with a gradient of 0.5% to 5% methanol in DCM, to provide 4-(2-fluoropyridin-3-yl)-2-methylpyridine. [M+1]=189.0.

Workup

  1. customUpon completion, the solvents were evaporated
  2. customchromatographed through a Biotage™ pre-packed silica gel column (40S)
  3. washeluting with a gradient of 0.5% to 5% methanol in DCM

Sources & evidence

ORD record
ord-85ea96b7b6244ba8b2f8b4b4153016ce
Source dataset
uspto-grants-2014_06
Patent number
US08759532B2

Linked notes

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