Hydrochloric Acid → 2-Chloro-6-(2,4-difluorophenylthio)nicotinonitrile

HRID 1048783Notes

Reaction equation

HRID 1048783 reaction equation
[OH-].[K+].[F:3][C:4]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:5]=1[SH:11].[Cl:12][C:13]1[N:20]=[C:19](Cl)[CH:18]=[CH:17][C:14]=1[C:15]#[N:16].Cl>C(O)C.O>[Cl:12][C:13]1[N:20]=[C:19]([S:11][C:5]2[CH:6]=[CH:7][C:8]([F:10])=[CH:9][C:4]=2[F:3])[CH:18]=[CH:17][C:14]=1[C:15]#[N:16]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 27370732,4-Difluorobenzene-1-thiolHCID 126055382,6-Dichloropyridine-3-carbonitrile

Product 1

HCID 866805632-Chloro-6-(2,4-difluorophenylthio)nicotinonitrileYield 66%

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent3×HCID 962WaterSolvent

Procedure

A solution of 362 mg (1.05 eq) of potassium hydroxide in 10 mL of ethanol is added, under nitrogen, to a solution of 698 μL (6.16 mmol) of 2,4-difluorobenzenethiol in 30 mL of ethanol. The reaction medium is stirred at room temperature for 15 minutes and then cooled in ice before adding a solution of 1.015 g (0.95 eq) of 2,6-dichloronicotinonitrile in 30 mL of ethanol. The reaction medium is stirred for 2 hours at 0-5° C. 63 ml, of a 0.1N HCl solution is added to stop the reaction. Water is added and the producted is extracted with ethyl acetate. The organic phase is dried on anhydrous magnesium sulfate, filtered and evaporated. The residue is purified by silica gel chromatography (eluent: cyclohexane/ethyl acetate 94:6) to yield 1.09 g (66%) of 2-chloro-6-(2,4-difluorophenylthio)-nicotinonitrile in the form of a white solid.

Workup

  1. temperaturecooled in ice
  2. stirringThe reaction medium is stirred for 2 hours at 0-5° C
  3. customthe reaction
  4. extractionthe producted is extracted with ethyl acetate
  5. dry with materialThe organic phase is dried on anhydrous magnesium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue is purified by silica gel chromatography (eluent: cyclohexane/ethyl acetate 94:6)

Sources & evidence

ORD record
ord-ce38ebebb00c4ee2bfbed09c687c53e8
Source dataset
uspto-grants-2016_07
Patent number
US09381195B2

Reaction notes

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