Acetone Cyanohydrin → HCID 178432828, compound

HRID 2180904Notes

Reaction equation

HRID 2180904 reaction equation
[CH3:1][C:2]1[N:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.C(N(CC)CC)C.[CH3:22][C:23]1([CH3:31])[CH2:28][CH2:27][C:26](=[O:29])[CH2:25][C:24]1=[O:30].CC(C)(O)C#N>C(Cl)(=O)C(Cl)=O.CN(C)C=O.C(#N)C>[OH:30][C:24]1[C:23]([CH3:31])([CH3:22])[CH2:28][CH2:27][C:26](=[O:29])[C:25]=1[C:4]([C:3]1[C:2]([CH3:1])=[N:10][C:9]([C:11]([F:14])([F:13])[F:12])=[CH:8][CH:7]=1)=[O:6]

Participants

8

Reactant 4

HCID 6406Acetone CyanohydrinHCID 8471Triethylamine2×HCID 1363601,3-Cyclohexanedione, 4,4-dimethyl-HCID 27756832-Methyl-6-(trifluoromethyl)nicotinic acid

Product 1

HCID 178432828HCID 178432828, compoundYield 64.2%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6342AcetonitrileSolventHCID 65578Oxalyl chlorideSolvent

Procedure

The 2-methyl-6-trifluoromethyl-nicotinic acid (1.026 g, 0.005 mol) obtained is dissolved in 20 ml of oxalyl chloride. Three drops of dimethylformamide are added and the mixture is refluxed for 1 hour. The mixture is then concentrated by evaporation using a rotary evaporator and the residue (2-methyl-6-trifluoromethyl-nicotinoyl chloride) is taken up in 100 ml of methylene-chloride. At a temperature of 0° C., 1.6 ml (0.0115 mol) of triethylamine and 0.7 g (0.005 mol) 4,4-dimethyl-cyclohexane-1,3-dione are added. After 2 hours at a temperature of 22° C., the solvent is removed using a vacuum rotary evaporator, the residue that remains is dissolved in 55 ml of acetonitrile and, for rearrangement of the intermediate, 0.15 ml (0.0016 mol) of acetone cyanohydrin and 0.79 ml (0.0057 mol) of triethylamine are added. After stirring for four hours at room temperature, the reaction solution is concentrated by evaporation. The syrup that remains is chromatographed on silica gel. The light-yellow, viscous oil obtained by eluting with a mixture of toluene, ethyl alcohol, dioxane, triethylamine and water (100:40:20:20:5 parts by volume) (Rf=0.39 based on the said mixture as mobile phase) is dissolved in dichloromethane and washed with 75 ml of hydrochloric acid 5% and 75 ml of water in succession. After drying the organic solution with Na2SO4, concentration by evaporation yields 1.05 g (63%) of pure title compound.

Workup

  1. temperaturethe mixture is refluxed for 1 hour
  2. concentrationThe mixture is then concentrated by evaporation
  3. customa rotary evaporator
  4. customthe solvent is removed
  5. customa vacuum rotary evaporator
  6. additionare added
  7. concentrationthe reaction solution is concentrated by evaporation
  8. customThe syrup that remains is chromatographed on silica gel
  9. customThe light-yellow, viscous oil obtained
  10. washby eluting with a mixture of toluene, ethyl alcohol, dioxane, triethylamine and water (100:40:20:20:5 parts by volume) (Rf=0.39
  11. dissolutionis dissolved in dichloromethane
  12. washwashed with 75 ml of hydrochloric acid 5% and 75 ml of water in succession
  13. customAfter drying the organic solution
  14. concentrationwith Na2SO4, concentration
  15. customby evaporation

Sources & evidence

ORD record
ord-bd078e8d19fd4b9db7ea893ddfa52563
Source dataset
uspto-grants-2005_05
Patent number
US06890885B2

Reaction notes

Loading…