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

HRID 1096688Notes

Reaction equation

HRID 1096688 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:16][C:17]([C:19]1[N:23]([CH3:24])[N:22]=[C:21]([CH3:25])[C:20]=1[CH3:26])=O)C.C(OCCOCCO)CCC.CO.C[O-].[Na+]>O.CCCCCCC>[O:16]=[C:17]([C:19]1[N:23]([CH3:24])[N:22]=[C:21]([CH3:25])[C:20]=1[CH3:26])[CH:11]([C:8]1[CH:7]=[CH:6][C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])=[CH:10][CH:9]=1)[C:12]#[N:13]

Participants

7

Reactant 4

HCID 8177Diethylene Glycol Monobutyl EtherHCID 76784(4-tert-Butylphenyl)acetonitrileHCID 9855653Ethyl 1,3,4-trimethyl-1H-pyrazole-5-carboxylateHCID 23694274Sodium methanolate methanol

Product 1

HCID 119839523-Oxo-2-(4-tert-butylphenyl)-3-(1,3,4-trimethylpyrazol-5-yl)propionitrileYield 85.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8900HeptaneSolvent

Conditions

Temperature
92.5 °C

Procedure

In a 2000 ml-reaction flask equipped with a rectification column and a separating tank, 83.7 g (483 mmol) of 4-tert-butylphenylacetonitrile, 80.0 g (439 mmol) of 1,3,4-trimethylpyrazol-5-carboxylic acid ethyl ester, 640 g of heptane, and 160 g of diethylene glycol monobutyl 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, 93.2 g (482 mmol) of 28% sodium methoxide methanol solution was added dropwise over 3 hours, and the resulting mixture was further reacted for 10 hours. After cooling to 30° C. or less, 600 g of water was added to separate out heptane phase, and the resulting aqueous phase was washed with 160 g of heptane and 400 g of toluene was added, then pH was adjusted to 7 with 35% hydrochloric acid. After separating into phases, the toluene phase was washed two times with 160 g of water to obtain a toluene solution containing 116 g (yield 85.1%) of 3-oxo-2-(4-tert-butylphenyl)-3-(1,3,4-trimethylpyrazol-5-yl) propionitrile. Toluene was distilled off under a reduced pressure, then 120 g of di-n-butyl ether was added and completely dissolved therein at a temperature of 120° C. Thereafter, the solution was cooled to 20° C., the resulting crystal was further dispersed in 150 g of di-n-butylether, 200 g of n-hexane was added therein and stirred at 10° C. for 1 hour. The resulting crystal was filtered and washed with 150 g of n-hexane to obtain 92.3 g of 3-oxo-2-(4-tert-butyl phenyl)-3-(1,3,4-trimethylpyrazol-5-yl) propionitrile (melting point 178° C.).

Workup

  1. customIn a 2000 ml-reaction flask
  2. customequipped with a rectification column
  3. temperatureThe temperature was maintained
  4. customthe resulting mixture was further reacted for 10 hours
  5. temperatureAfter cooling to 30° C. or less
  6. customto separate out heptane phase
  7. washthe resulting aqueous phase was washed with 160 g of heptane and 400 g of toluene
  8. additionwas added
  9. customAfter separating into phases
  10. washthe toluene phase was washed two times with 160 g of water
  11. customto obtain a toluene solution

Sources & evidence

ORD record
ord-71b3826d4ba548c998169510f6b9ace4
Source dataset
uspto-grants-2012_03
Patent number
US08138368B2

Reaction notes

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