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

HRID 1027964Notes

Reaction equation

HRID 1027964 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]>CN(C=O)C.[NH4+].[Cl-].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 3

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

Product 1

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

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 25517Ammonium ChlorideSolvent

Procedure

1,3 Equivalents of NaH (4.9 g, 0.124 mol) were dissolved in 50 mL of DMF under a blanket of nitrogen. Following the addition of 1.2 equivalents of cyclohexanethiol (14.2 mL, 0.116 mol), the mixture was stirred at room temperature over a period of 1.5 h. The resulting suspension was cooled to 10° C. and added dropwise to 1 equivalent of 2-chloro-6-(trifluoromethyl)nicotinonitrile (20 g, 0.096 mol) in 50 mL of DMF and stirred over a period of 2 h at room temperature. The reaction mixture was diluted with sat. aq. NH4Cl solution and with 1 L of water and extracted with EA (3×200 mL). The combined organic phases were washed with sat. aq. NaCl solution, dried over MgSO4 and concentrated in vacuo. Column chromatographic purification (silica gel 100-200 mesh, eluent: 2% EA in hexane) produced 26 g (93.8%) of product.

Workup

  1. temperatureThe resulting suspension was cooled to 10° C.
  2. stirringstirred over a period of 2 h at room temperature
  3. extractionextracted with EA (3×200 mL)
  4. washThe combined organic phases were washed with sat. aq. NaCl solution
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customColumn chromatographic purification (silica gel 100-200 mesh, eluent: 2% EA in hexane)

Sources & evidence

ORD record
ord-54b61145fbd5426a9fe541990f78b7ad
Source dataset
uspto-grants-2014_05
Patent number
US08735426B2

Reaction notes

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