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

HRID 1631699Notes

Reaction equation

HRID 1631699 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 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 RT 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 RT. To the reaction mixture there was added sat. aq. NH4Cl soln. and the mixture was diluted 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, eluant: 2% EA in hexane) yielded 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 RT
  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, eluant: 2% EA in hexane)

Sources & evidence

ORD record
ord-21d28822f36b4bb78ff6ab23ec6657d9
Source dataset
uspto-grants-2014_07
Patent number
US08791268B2

Reaction notes

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