Acetone Cyanohydrin → HCID 178496212, compound

HRID 2224015Notes

Reaction equation

HRID 2224015 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][O:5][CH2:6][C:7]1[N:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[CH:12][C:8]=1[C:9]([OH:11])=O.C(N(CC)CC)C.[CH3:27][N:28]1[C:32](=[O:33])[CH2:31][C:30]([CH3:34])=[N:29]1.CC(C)(O)C#N>C(Cl)(=O)C(Cl)=O.CN(C)C=O>[OH:33][C:32]1[N:28]([CH3:27])[N:29]=[C:30]([CH3:34])[C:31]=1[C:9]([C:8]1[C:7]([CH2:6][O:5][CH2:4][CH2:3][O:2][CH3:1])=[N:15][C:14]([C:16]([F:19])([F:18])[F:17])=[CH:13][CH:12]=1)=[O:11]

Participants

7

Reactant 4

HCID 6406Acetone CyanohydrinHCID 8471Triethylamine2×HCID 176733H-Pyrazol-3-one, 2,4-dihydro-2,5-dimethyl-HCID 113349532-(2-Methoxy-ethoxymethyl)-6-trifluoromethyl-nicotinic acid

Product 1

HCID 178496212HCID 178496212, compoundYield 62.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 65578Oxalyl chlorideSolvent

Procedure

1.0 g (0.004 mol) of 2-(2-methoxyethoxymethyl)-6-trifluoromethylnicotinic acid is dissolved in 10 ml of oxalyl chloride. Three drops of dimethylformamide are added, and the mixture is stirred at room temperature for 1 hour. The mixture is then concentrated using a rotary evaporator, and the residue (2-(2-methoxyethoxymethyl)-6-trifluoromethylnicotinoyl chloride) is taken up in 10 ml of methylene chloride. At a temperature of 0° C., 0.84 ml (0.006 mol) of triethylamine and 0.45 g (0.004 mol) of 2,5-dimethyl-2,4-dihydropyrazol-3-one are added. After 2 hours at a temperature of 22° C., the solvent is removed using a vacuum rotary evaporator, and the residue that remains is dissolved in 10 ml of acetonitrile and, to rearrange the intermediate (2,5-dimethyl-2H-pyrazol-3-yl 2-(2-methoxyethoxymethyl)-6-trifluoromethylnicotinate), admixed with 0.1 ml of acetone cyanohydrin and 1.13 ml (0.008 mol) of triethylamine. The reaction solution is stirred at room temperature for four hours and then concentrated. The syrup that remains is chromatographed on silica gel. The viscous oil obtained by eluting with a mixture of toluene, ethyl alcohol, dioxane, triethylamine and water (100:40:20:20:5 parts by volume) is dissolved in ethyl acetate and washed successively with 10% hydrochloric acid and water. The organic solution is dried over Na2SO4 and concentrated, giving 0.93 g of (5-hydroxy-1,3-dimethyl-1H-pyrazol-4-yl)-[2-(2-methoxyethoxymethyl)-6-trifluoromethylpyridin-3-yl]methanone in the form of a viscous oil. 1H NMR (300 MHz, CDCl3, 8 in ppm): 7.81, (d, J=6 Hz), 1H, 7.74, (d, J=6 Hz), 1H, 4.84, (s), 2H; 2H, 3.71, (s), 3H, 3.59, (t, J=6 Hz) 2H, 3.38, (dd, J 4.0, 3.0 Hz), 1H, 3.26, (s), 3H, 1.82 ppm, (s), 1H.

Workup

  1. concentrationThe mixture is then concentrated
  2. customa rotary evaporator
  3. waitAfter 2 hours at a temperature of 22° C.
  4. customthe solvent is removed
  5. customa vacuum rotary evaporator
  6. dissolutionthe residue that remains is dissolved in 10 ml of acetonitrile
  7. stirringThe reaction solution is stirred at room temperature for four hours
  8. concentrationconcentrated
  9. customThe syrup that remains is chromatographed on silica gel
  10. customThe viscous oil obtained
  11. washby eluting with a mixture of toluene, ethyl alcohol, dioxane, triethylamine and water (100:40:20:20:5 parts by volume)
  12. dissolutionis dissolved in ethyl acetate
  13. washwashed successively with 10% hydrochloric acid and water
  14. dry with materialThe organic solution is dried over Na2SO4
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-4830e79a0a744758b9c6383840ed0755
Source dataset
uspto-grants-2008_05
Patent number
US07378375B1

Reaction notes

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