Ammonium Chloride → 1-benzyl-3-benzyloxy-1H-pyrazol-4-ylacetonitrile

HRID 350015Notes

Reaction equation

HRID 350015 reaction equation
C1(C)C=CC(S([CH2:10][N+:11]#[C-])(=O)=O)=CC=1.CC(C)([O-])C.[K+].[CH2:20]([N:27]1[CH:31]=[C:30]([CH:32]=O)[C:29]([O:34][CH2:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)=[N:28]1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[Cl-].[NH4+]>C(COC)OC.CO>[CH2:20]([N:27]1[CH:31]=[C:30]([CH2:32][C:10]#[N:11])[C:29]([O:34][CH2:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)=[N:28]1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 161915Tosylmethyl isocyanideHCID 229307681-benzyl-3-(benzyloxy)-1H-pyrazole-4-carbaldehydeHCID 23665647Potassium tert-butoxide

Product 1

HCID 693145121-benzyl-3-benzyloxy-1H-pyrazol-4-ylacetonitrileYield 86.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 80711,2-DimethoxyethaneSolvent3×

Procedure

A solution of p-toluenesufonylmethylisocyanide (10.3 g) in dimethoxyethane (50 ml) was added to a mixture of potassium t-butoxide (11.2 g) and dimethoxyethane (50 ml) at −78° C., and the mixture was stirred for 5 minutes. A solution of 1-benzyl-3-benzyloxy-1H-pyrazole-4-carbaldehyde (14.6 g) in dimethoxyethane (50 ml) was added to the mixture. After stirring at the same temperature for 1 hour, the mixture was stirred for 1 hour while raising the temperature. Methanol (150 ml) was added to the mixture, which was refluxed for 1 hour. After cooling, the reaction solution was poured into saturated aqueous ammonium chloride solution, which was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride solution, dried (MgSO4), and concentrated. The residue was subjected to silica gel column chromatography to obtain 1-benzyl-3-benzyloxy-1H-pyrazol-4-ylacetonitrile (13.1 g, yield 86%) as a colorless oily substance from the fraction eluted with ethyl acetate-hexane (1:3, volume ratio).

Workup

  1. stirringAfter stirring at the same temperature for 1 hour
  2. stirringthe mixture was stirred for 1 hour
  3. temperaturewhile raising the temperature
  4. temperaturewas refluxed for 1 hour
  5. temperatureAfter cooling
  6. extractionwas extracted with ethyl acetate
  7. washThe ethyl acetate layer was washed with saturated aqueous sodium chloride solution
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-65956e39d6714037a78b49badad82e15
Source dataset
uspto-grants-2007_02
Patent number
US07179823B1

Reaction notes

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