Ethyl Acetate → 4-Chloro-6-(trifluoromethyl)-3-pyridineacetonitrile

HRID 623315Notes

Reaction equation

HRID 623315 reaction equation
C[Si]([C:5]#[N:6])(C)C.[Cl:7][C:8]1[C:13]([CH2:14]Cl)=[CH:12][N:11]=[C:10]([C:16]([F:19])([F:18])[F:17])[CH:9]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.CCOC(C)=O>C(#N)C>[Cl:7][C:8]1[CH:9]=[C:10]([C:16]([F:19])([F:17])[F:18])[N:11]=[CH:12][C:13]=1[CH2:14][C:5]#[N:6]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 82115Trimethylsilyl cyanideHCID 2724141Tetrabutylammonium FluorideHCID 72212581HCID 72212581, compound

Product 1

HCID 867325444-Chloro-6-(trifluoromethyl)-3-pyridineacetonitrileYield 65.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
25 °C

Procedure

Trimethylsilylcyanid (TMSCN) (69.3 g, 0.7 mol) was added to a solution of 4-chloro-5-(chloromethyl)-2-(trifluoromethyl)pyridine (Int-13) (80 g, 0.348 mol) and Tetra-n-butylammoniumfluoride (129.5 g, 0.7 mol) in acetonitrile (1.5 L) slowly. Then the mixture was stirred at 20-30° C. for 2 hours. Thin layer chromatography (petroleum ether: EtOAc=3:1) showed all of starting material was consumed. The mixture was concentrated and the residue was purified by silica gel chromatography eluted with petroleum ether: EtOAc=20:1˜3:1 to yield [4-chloro-6-(trifluoromethyl)pyridin-3-yl]acetonitrile (Int-14) (50 g, 60% from NMR, 39% of yield) as yellow syrup.

Workup

  1. customwas consumed
  2. concentrationThe mixture was concentrated
  3. customthe residue was purified by silica gel chromatography
  4. washeluted with petroleum ether

Sources & evidence

ORD record
ord-f2f344c87c9d4a30a72092f6ede91c52
Source dataset
uspto-grants-2016_04
Patent number
US09301526B2

Reaction notes

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