3,5-Difluoropyridine → HCID 67774589, compound

HRID 533403Notes

Reaction equation

HRID 533403 reaction equation
C([Li])CCC.[F:6][C:7]1[CH:8]=[N:9][CH:10]=[C:11]([F:13])[CH:12]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC(C)C)=CC=CC=2OC(C)C)CCCCC1.[CH3:47][C:48]1[C:57]([CH3:58])=[C:56](OS(C(F)(F)F)(=O)=O)[C:55]2[C:50](=[CH:51][CH:52]=[C:53]([C:67]([O:69][CH2:70][CH3:71])=[O:68])[CH:54]=2)[N:49]=1>[Cl-].[Zn+2].[Cl-].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1COCC1>[F:6][C:7]1[CH:8]=[N:9][CH:10]=[C:11]([F:13])[C:12]=1[C:56]1[C:55]2[C:50](=[CH:51][CH:52]=[C:53]([C:67]([O:69][CH2:70][CH3:71])=[O:68])[CH:54]=2)[N:49]=[C:48]([CH3:47])[C:57]=1[CH3:58]

Participants

8

Reactant 4

HCID 6428203,5-DifluoropyridineHCID 162179852-Dicyclohexylphosphino-2',6'-diisopropoxybiphenylHCID 86666252HCID 86666252, compoundHCID 178418339Butyllithium

Product 1

HCID 67774589HCID 67774589, compoundYield 18.7%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Under argon gas atmosphere, n-butyllithium (1.6 M THF solution, 1.3 mL) was added dropwise to a mixture of 3,5-difluoropyridine (238 mg) and THF (4 mL) at −78° C., followed by stirring at the same temperature for one hour. Then, zinc chloride (0.5 M THF solution, 3.8 mL) was slowly added stirried at the same temperature for 30 minutes and further for an additional hour at room temperature. Tris(dibenzylideneacetone)dipalladium (73 mg), 2-dicyclohexylphosphino-2′,6′-diisopropoxybiphenyl (148 mg), and ethyl 2,3-dimethyl-4-{[(trifluoromethyl)sulfonyl]oxy}quinoline-6-carboxylate (300 mg), were added to the reaction mixture and heated under stirring in an oil bath at 70° C. for 15 hours. The reaction mixture was returned to room temperature, and the insoluble materials were separated by filtration. Then, the precipitate was concentrated under reduced pressure, and the resulting residue was purified under silica gel column chromatography (hexane/ethyl acetate) to obtain ethyl 4-(3,5-difluoropyridin-4-yl)-2,3-dimethylquinoline-6-carboxylate (51 mg).

Workup

  1. waitstirried at the same temperature for 30 minutes and further for an additional hour at room temperature
  2. temperatureheated
  3. stirringunder stirring in an oil bath at 70° C. for 15 hours
  4. customwas returned to room temperature
  5. customthe insoluble materials were separated by filtration
  6. concentrationThen, the precipitate was concentrated under reduced pressure
  7. customthe resulting residue was purified under silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-c3cc5c65d471495c9c6e1bb6a857f58d
Source dataset
uspto-grants-2014_10
Patent number
US08853242B2

Reaction notes

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