Cesium fluoride → HCID 67026888, compound

HRID 2113416Notes

Reaction equation

HRID 2113416 reaction equation
CB(O)O.[F-].[Cs+].[C:7]1(P(C2C=CC=CC=2)CCCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[NH2:37][C:38]1[C:43]([F:44])=[C:42](Cl)[N:41]=[C:40]([C:46]([O:48][CH3:49])=[O:47])[C:39]=1[Cl:50]>C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C(N(CC)CC)C>[NH2:37][C:38]1[C:43]([F:44])=[C:42]([CH3:7])[N:41]=[C:40]([C:46]([O:48][CH3:49])=[O:47])[C:39]=1[Cl:50]

Participants

9

Reactant 4

HCID 25953Cesium fluorideHCID 821241,4-Bis(diphenylphosphino)butaneHCID 139377Methylboronic AcidHCID 22677265Methyl 4-amino-3,6-dichloro-5-fluoropicolinate

Product 1

HCID 67026888HCID 67026888, compoundYield 500%

Reagents, catalysts & solvents 4

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

Procedure

A solution of methylboronic acid (0.17 g, 2.93 mmol), cesium fluoride (0.95 g, 6.27 mmol), 1,4-bis(diphenylphosphino)butane (0.09 g, 0.21 mmol), methyl 4-amino-3,6-dichloro-5-fluoropyridine-2-carboxylate (0.50 g, 2.09 mmol) and triethylamine (1 mL) in acetonitrile (20 mL) was purged for 15 minutes with nitrogen. Palladium acetate (0.05 g, 0.21 mmol) was then added and the reaction mixture heated under reflux overnight. After cooling, water was added and the mixture extracted with ethyl acetate. The organic layer was washed with brine, dried (MgSO4), and concentrated. The residue was purified by column chromatography (33% ethyl acetate in hexane) to give methyl 4-amino-3-chloro-5-fluoro-6-methylpyridine-2-carboxylate (0.23 g, 1.05 mmol), mp 113-114° C.

Workup

  1. temperaturethe reaction mixture heated
  2. temperatureunder reflux overnight
  3. temperatureAfter cooling
  4. extractionthe mixture extracted with ethyl acetate
  5. washThe organic layer was washed with brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography (33% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-d5e48e6c275046029e0bf282ebf306cb
Source dataset
uspto-grants-2008_10
Patent number
US07432227B2

Reaction notes

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