Ammonium Chloride → [1-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyl]-3-(2-thienyl)-1H-pyrazol-4-yl]acetonitrile

HRID 350024Notes

Reaction equation

HRID 350024 reaction equation
C1(C)C=CC(S([CH2:10][N+:11]#[C-])(=O)=O)=CC=1.CC(C)([O-])C.[K+].[CH3:20][C:21]1[O:25][C:24]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[N:23][C:22]=1[CH2:32][O:33][C:34]1[CH:52]=[CH:51][C:37]([CH2:38][N:39]2[CH:43]=[C:42]([CH:44]=O)[C:41]([C:46]3[S:47][CH:48]=[CH:49][CH:50]=3)=[N:40]2)=[CH:36][CH:35]=1.[Cl-].[NH4+]>C(COC)OC.CO>[CH3:20][C:21]1[O:25][C:24]([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)=[N:23][C:22]=1[CH2:32][O:33][C:34]1[CH:52]=[CH:51][C:37]([CH2:38][N:39]2[CH:43]=[C:42]([CH2:44][C:10]#[N:11])[C:41]([C:46]3[S:47][CH:48]=[CH:49][CH:50]=3)=[N:40]2)=[CH:36][CH:35]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 161915Tosylmethyl isocyanideHCID 230248961-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyl]-3-(2-thienyl)-1H-pyrazole-4-carbaldehydeHCID 23665647Potassium tert-butoxide

Product 1

HCID 69421547[1-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyl]-3-(2-thienyl)-1H-pyrazol-4-yl]acetonitrileYield 82.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 80711,2-DimethoxyethaneSolvent3×

Procedure

A solution of p-toluenesulfonylmethylisocyanide (0.95 g) in dimethoxyethane (10 ml) was added to a mixture of potassium tert-butoxide (1.01 g) and dimethoxyethane (10 ml) at −78° C., and the mixture was stirred for 5 minutes. A solution of 1-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyl]-3-(2-thienyl)-1H-pyrazole-4-carbaldehyde (2.01 g) in dimethoxyethane (20 ml) was added to the mixture, and then stirred at the same temperature for 1 hour, and at room temperature for 1 hour. Methanol (40 ml) was added to the mixture, and reflux was conducted for 1 hour. After cooling, the reaction mixture was poured into saturated aqueous ammonium chloride solution, and 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 chromatography to obtain [1-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyl]-3-(2-thienyl)-1H-pyrazol-4-yl]acetonitrile (1.69 g, yield: 78%) as a colorless oily substance from the fraction eluted with ethyl acetate-hexane (1:3, volume ratio).

Workup

  1. stirringstirred at the same temperature for 1 hour
  2. waitat room temperature for 1 hour
  3. temperaturereflux
  4. waitwas conducted for 1 hour
  5. temperatureAfter cooling
  6. extractionextracted 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-6bd7ee6e00b64136bec2f2346936d748
Source dataset
uspto-grants-2007_02
Patent number
US07179823B1

Reaction notes

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