Potassium Phosphate, Tribasic → 2-(2,3-Difluoro-6-methoxy-phenyl)-N-methoxy-N-methyl-isonicotinamide

HRID 1909016Notes

Reaction equation

HRID 1909016 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:11]=[CH:12][N:13]=1)[C:5]([N:7]([O:9][CH3:10])[CH3:8])=[O:6].[F:14][C:15]1[C:20]([F:21])=[CH:19][CH:18]=[C:17]([O:22][CH3:23])[C:16]=1B(O)O.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[F:14][C:15]1[C:20]([F:21])=[CH:19][CH:18]=[C:17]([O:22][CH3:23])[C:16]=1[C:2]1[CH:3]=[C:4]([CH:11]=[CH:12][N:13]=1)[C:5]([N:7]([O:9][CH3:10])[CH3:8])=[O:6]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 43727862,3-Difluoro-6-methoxyphenylboronic acidHCID 448186542-Bromo-N-methoxy-N-methylisonicotinamide

Product 1

HCID 866643432-(2,3-Difluoro-6-methoxy-phenyl)-N-methoxy-N-methyl-isonicotinamideYield 23%

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A flask containing 2-bromo-N-methoxy-N-methyl-isonicotinamide (Example 25, using method 2) (3.0 g, 12.2 mmol) 2,3-difluoro-6-methoxyphenylboronic acid (4.6 g, 24.4 mmol)) and 2M aqueous K3PO4 (15 mL, 30.6 mmol) in 1,4-dioxane (40 mL) was successively evacuated and flushed with nitrogen. Pd(PtBu3)2 (268 mg, 0.48 mmol) was then added and the mixture heated at 90° C. for 2 hours. The mixture was cooled, concentrated in vacuo and then partitioned between EtOAc and sat. aqueous NaHCO3 solution. The organic layer was washed with brine, dried (MgSO4) and concentrated in vacuo. Purification by SiO2 chromatography (eluting with 30-100% EtOAc/hexane) gave the title compound (0.856 g, 23%). MS(ESI) m/z 309 (M+H)+

Workup

  1. customwas successively evacuated
  2. customflushed with nitrogen
  3. temperatureThe mixture was cooled
  4. concentrationconcentrated in vacuo
  5. custompartitioned between EtOAc and sat. aqueous NaHCO3 solution
  6. washThe organic layer was washed with brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customPurification
  10. washby SiO2 chromatography (eluting with 30-100% EtOAc/hexane)

Sources & evidence

ORD record
ord-8eaede80015a49b7976a59d2cffffad1
Source dataset
uspto-grants-2013_12
Patent number
US08598217B2

Reaction notes

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