Cesium fluoride → Methyl 4-amino-3-chloro-6-(3,4-dimethylphenyl)pyridine-2-carboxylate

HRID 1837453Notes

Reaction equation

HRID 1837453 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[CH:6][C:7]=1[CH3:8].[F-].[Cs+].C1(P(C2C=CC=CC=2)CCCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[NH2:44][C:45]1[CH:50]=[C:49](Cl)[N:48]=[C:47]([C:52]([O:54][CH3:55])=[O:53])[C:46]=1[Cl:56]>C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C(N(CC)CC)C>[NH2:44][C:45]1[CH:50]=[C:49]([C:4]2[CH:5]=[CH:6][C:7]([CH3:8])=[C:2]([CH3:1])[CH:3]=2)[N:48]=[C:47]([C:52]([O:54][CH3:55])=[O:53])[C:46]=1[Cl:56]

Participants

9

Reactant 4

HCID 25953Cesium fluorideHCID 821241,4-Bis(diphenylphosphino)butaneHCID 27343483,4-Dimethylphenylboronic acidHCID 22677331Methyl 4-amino-3,6-dichloropyridine-2-carboxylate

Product 1

HCID 22677522Methyl 4-amino-3-chloro-6-(3,4-dimethylphenyl)pyridine-2-carboxylateYield 50%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8471TriethylamineSolvent

Procedure

A solution of 3,4-dimethylphenylboronic acid (2.1 g, 14.0 mmol), cesium fluoride (6.3 g, 41.5 mmol), 1,4-bis(diphenylphosphino)butane (0.5 g, 1.2 mmol), methyl 4-amino-3,6-dichloropyridine-2-carboxylate (2.5 g, 10.0 mmol) and triethylamine (5 mL) in acetonitrile (100 mL) was sparged for thirty minutes with nitrogen. Palladium acetate (0.3 g, 1.2 mmol) was added and the reaction mixture heated under reflux for three hours. After cooling water (200 mL) was added and the mixture extracted with ethyl acetate (2×100 mL). The organic layer was washed with brine (100 mL), dried (NaSO4), and concentrated. The residue was purified by column chromatography (33 percent ethyl acetate in hexane) to give methyl 4-amino-3-chloro-6-(3,4-dimethylphenyl)pyridine-2-carboxylate (1.4 g, 5.0 mmol), mp 154-156° C.

Workup

  1. temperaturethe reaction mixture heated
  2. temperatureunder reflux for three hours
  3. additionwas added
  4. extractionthe mixture extracted with ethyl acetate (2×100 mL)
  5. washThe organic layer was washed with brine (100 mL)
  6. dry with materialdried (NaSO4)
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography (33 percent ethyl acetate in hexane)

Sources & evidence

ORD record
ord-009b1d8a67404275b1c35f58e9a27735
Source dataset
uspto-grants-2004_08
Patent number
US06784137B2

Reaction notes

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