Potassium Phosphate, Tribasic → 8-(4-(2,3-Difluorophenyl)pyridin-2-yl)-2-methylbenzofuro[2,3-b]pyridine

HRID 1844934Notes

Reaction equation

HRID 1844934 reaction equation
[CH3:1][C:2]1[N:7]=[C:6]2[O:8][C:9]3[C:14](B4OC(C)(C)C(C)(C)O4)=[CH:13][CH:12]=[CH:11][C:10]=3[C:5]2=[CH:4][CH:3]=1.Cl[C:25]1[CH:30]=[C:29]([C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([F:37])[C:32]=2[F:38])[CH:28]=[CH:27][N:26]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O.C1(C)C=CC=CC=1>[F:38][C:32]1[C:33]([F:37])=[CH:34][CH:35]=[CH:36][C:31]=1[C:29]1[CH:28]=[CH:27][N:26]=[C:25]([C:14]2[C:9]3[O:8][C:6]4[C:5]([C:10]=3[CH:11]=[CH:12][CH:13]=2)=[CH:4][CH:3]=[C:2]([CH3:1])[N:7]=4)[CH:30]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 866319712-Chloro-4-(2,3-difluorophenyl)pyridineHCID 901214882-Methyl-8-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuro[2,3-b]pyridine

Product 1

HCID 901215948-(4-(2,3-Difluorophenyl)pyridin-2-yl)-2-methylbenzofuro[2,3-b]pyridineYield 35.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

2-methyl-8-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuro[2,3-b]pyridine (2.8 g, 9.06 mmol), 2-chloro-4-(2,3-difluorophenyl)pyridine (2.452 g, 10.87 mmol), tris(dibenzylideneacetone)palladium(0) (0.166 g, 0.181 mmol) and 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (0.297 g, 0.725 mmol) were charged into the reaction mixture with 200 mL of toluene. Potassium phosphate tribasic (5.76 g, 27.2 mmol) was dissolved in 25 mL of water then was charged into the reaction mixture. This mixture was degassed then heated to reflux for 18 hours. The reaction mixture was cooled to room temperature. The toluene layer was separated and was dried over magnesium sulfate. This mixture was filtered and concentrated under vacuum. The crude residue was passed through a silica gel column using 15-22.5% ethyl acetate/heptanes. The clean product fractions were evaporated under reduced pressure yielding 8-(4-(2,3-difluorophenyl)pyridin-2-yl)-2-methylbenzofuro[2,3-b]pyridine (1.2 g, 3.22 mmol, 35.6% yield) as a white solid.

Workup

  1. additionthen was charged into the reaction mixture
  2. customThis mixture was degassed
  3. temperaturethen heated
  4. temperatureto reflux for 18 hours
  5. customThe toluene layer was separated
  6. dry with materialwas dried over magnesium sulfate
  7. filtrationThis mixture was filtered
  8. concentrationconcentrated under vacuum
  9. customThe clean product fractions were evaporated under reduced pressure

Sources & evidence

ORD record
ord-19669df0d28e48259e4176a87c1abffa
Source dataset
uspto-grants-2015_02
Patent number
US08946697B1

Reaction notes

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