Water → 6-Methoxy-2-methyl-3-(5-methyl-4-isoxazolyl)pyridine

HRID 900068Notes

Reaction equation

HRID 900068 reaction equation
I[C:2]1[CH:3]=[N:4][O:5][C:6]=1[CH3:7].[CH3:8][O:9][C:10]1[N:15]=[C:14]([CH3:16])[C:13](B(O)O)=[CH:12][CH:11]=1.C(=O)(O)[O-].[Na+].O>COCCOC>[CH3:16][C:14]1[C:13]([C:2]2[CH:3]=[N:4][O:5][C:6]=2[CH3:7])=[CH:12][CH:11]=[C:10]([O:9][CH3:8])[N:15]=1

Participants

6

Reactant 4

HCID 962WaterHCID 516892Sodium BicarbonateHCID 27630842-Methyl-6-methoxypyridine-3-boronic acidHCID 27954614-Iodo-5-methylisoxazole

Product 1

HCID 210719306-Methoxy-2-methyl-3-(5-methyl-4-isoxazolyl)pyridineYield 40.2%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of 4-iodo-5-methylisoxazole (18.2 g, 87 mmol), 6-methoxy-2-methylpyridine-3-boronic acid (14.6 g, 87 mmol), sodium bicarbonate (22.0 g, 262 mmol), water (150 mL) and DME (150 mL) was degassed three times with stirring by the application of a vacuum and then introduction of a nitrogen atmosphere. [1,1-Bis(diphenylphosphino)ferrocene]-dichloropalladium (II) (2.14 g, 2.6 mmol) was added in one portion. The reaction mixture was degassed as before. The reaction mixture was then stirred at 80° C. for 4 h, then it was cooled to ambient temperature. Three extractions with EtOAc, drying the combined organic layers over MgSO4, filtration and removal of solvent in vacuo afforded an oil. Flash chromatography (EtOAc:hexane::1:9) and removal of solvent in vacuo from the desired fractions gave the product (7.15 g): 1H-NMR(CDCl3, 300 MHz): δ 8.16 (s, 1H), 7.33 (d, 1H, J=8), 6.63 (d, 1H, J=8), 3.95 (s, 3H), 2.35 (s, 6H); APCI+-MS: 205 (M++H).

Workup

  1. customwas degassed three times
  2. customThe reaction mixture was degassed as before
  3. stirringThe reaction mixture was then stirred at 80° C. for 4 h
  4. extractionThree extractions with EtOAc
  5. customdrying the combined organic layers
  6. filtrationover MgSO4, filtration and removal of solvent in vacuo
  7. customafforded an oil
  8. customFlash chromatography (EtOAc:hexane::1:9) and removal of solvent in vacuo from the desired fractions

Sources & evidence

ORD record
ord-47cc0fee7ab841b68a62620b8ca85689
Source dataset
uspto-grants-2008_04
Patent number
US07358252B2

Reaction notes

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