Cyclohexanethiol → 2-(Cyclohexylthio)-6-(trifluoromethyl)nicotinonitrile

HRID 1626835Notes

Reaction equation

HRID 1626835 reaction equation
[H-].[Na+].[CH:3]1([SH:9])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.Cl[C:11]1[N:18]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:16]=[CH:15][C:12]=1[C:13]#[N:14].[NH4+].[Cl-]>CN(C=O)C.O>[CH:3]1([S:9][C:11]2[N:18]=[C:17]([C:19]([F:22])([F:20])[F:21])[CH:16]=[CH:15][C:12]=2[C:13]#[N:14])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1

Participants

7

Reactant 4

HCID 15290CyclohexanethiolHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 27784132-Chloro-6-(trifluoromethyl)nicotinonitrile

Product 1

HCID 598268632-(Cyclohexylthio)-6-(trifluoromethyl)nicotinonitrileYield 94.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

1.3 equivalents of NaH (4.9 g, 0.124 mol) were dissolved in 50 mL DMF under a nitrogen atmosphere. After the addition of 1.2 equivalents of cyclohexanethiol (14.2 mL, 0.116 mol) stirring was performed at RT for 1.5 h. The resultant suspension was cooled to 10° C. and 1 equivalent of 2-chloro-6-(trifluoromethyl)nicotinonitrile (20 g, 0.096 mol) in 50 mL DMF was added dropwise and stirred for 2 h at RT. The reaction mixture was combined with sat. aq. NH4Cl soln., diluted with 1 L of water and extracted repeatedly with EA (3×200 mL). The combined organic phases were washed with a sat. aq. NaCl soln., dried over MgSO4 and evaporated under a vacuum. Purification performed by column chromatography (silica gel, 100-200 mesh, eluent: 2% EA in hexane) resulted in 26 g (93.8%) of product.

Workup

  1. stirringstirred for 2 h at RT
  2. extractionextracted repeatedly with EA (3×200 mL)
  3. washThe combined organic phases were washed with a sat. aq. NaCl soln
  4. dry with material, dried over MgSO4
  5. customevaporated under a vacuum
  6. customPurification

Sources & evidence

ORD record
ord-ad209b79cc354729941d775c3e58999f
Source dataset
uspto-grants-2014_07
Patent number
US08785474B2

Reaction notes

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