Diethylene Glycol Monoethyl Ether → 3-Oxo-2-(4-tert-butylphenyl)-3-(1,3,4-trimethylpyrazol-5-yl)propionitrile

HRID 2190978Notes

Reaction equation

HRID 2190978 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([CH2:11][C:12]#[N:13])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C[O:15][C:16]([C:18]1[N:22]([CH3:23])[N:21]=[C:20]([CH3:24])[C:19]=1[CH3:25])=O.C(OCCOCCO)C.CO.C[O-].[Na+]>COCCOCCOC.CCCCCCC>[C:1]([C:5]1[CH:6]=[CH:7][C:8]([CH:11]([C:16]([C:18]2[N:22]([CH3:23])[N:21]=[C:20]([CH3:24])[C:19]=2[CH3:25])=[O:15])[C:12]#[N:13])=[CH:9][CH:10]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 8146Diethylene Glycol Monoethyl EtherHCID 76784(4-tert-Butylphenyl)acetonitrileHCID 23694274Sodium methanolate methanolHCID 45082645Methyl 1,3,4-trimethyl-1H-pyrazole-5-carboxylate

Product 1

HCID 119839523-Oxo-2-(4-tert-butylphenyl)-3-(1,3,4-trimethylpyrazol-5-yl)propionitrileYield 95.5%

Reagents, catalysts & solvents 2

HCID 8150DiglymeSolventHCID 8900HeptaneSolvent

Conditions

Temperature
92.5 °C

Procedure

In a 10 L-reaction flask equipped with a rectification column and a separating tank, 314 g (1.81 mol) of 4-tert-butylphenylacetonitrile, 274 g (1.65 mol) of 1,3,4-trimethylpyrazol-5-carboxylic acid methyl ester, 3000 g of heptane, 225 g of diethylene-glycol dimethyl ether, and 99 g of diethylene glycol monoethyl ether were added, the atmosphere was substituted with nitrogen, then azeotropic dehydration was carried out by heating at 90 to 95° C. for 1 hour. The temperature was maintained, 381 g (1.98 mol) of 28% sodium methoxide methanol solution was added dropwise over 13 hours, and the resulting mixture was further reacted for 10 hours. During this reaction, it is continued to remove alcohol separated in the phase under the heptane phase in the separating tank. After cooling to 30° C. or less, 3000 g of water was added to separate out heptane phase, and the resulting aqueous phase was further washed with 600 g of heptane to separate out heptane phase. A quantitative analysis of the obtained aqueous phase with liquid chromatography showed that the aqueous phase contained 486 g (yield 95.5%) of 2-(4-tert-butylphenyl)-3-(1,3,4-trimethyl-5-pyrazolyl)-3-oxopropionitrile. To the aqueous phase, 206 g (1.98 mol) of 35% hydrochloric acid was gradually added dropwise to be neutralized. After stirring for 1 hour, separated crystal was filtered, washed with 300 g of water, and then dried to obtain 475 g (yield 93.4%) of 3-oxo-2-(4-tert-butylphenyl)-3-(1,3,4-trimethylpyrazol-5-yl) propionitrile.

Workup

  1. customIn a 10 L-reaction flask
  2. customequipped with a rectification column
  3. temperatureThe temperature was maintained
  4. customthe resulting mixture was further reacted for 10 hours
  5. customDuring this reaction, it
  6. customto remove alcohol
  7. customseparated in the phase under the heptane phase in the separating tank
  8. temperatureAfter cooling to 30° C. or less
  9. addition3000 g of water was added
  10. customto separate out heptane phase
  11. washthe resulting aqueous phase was further washed with 600 g of heptane
  12. customto separate out heptane phase

Sources & evidence

ORD record
ord-73147f05885c49e195865601d1fbfc8c
Source dataset
uspto-grants-2012_12
Patent number
US08324420B2

Reaction notes

Loading…