Tetrahydrofuran → {3-[(4-{[2-(2-furyl)-5-methyl-1,3-oxazol-4-yl]methoxy}-3-methoxybenzyl)oxy]-1-phenyl-1H-pyrazol-4-yl}acetonitrile

HRID 2221813Notes

Reaction equation

HRID 2221813 reaction equation
CC(C)([O-])C.[K+].C1(C)C=CC(S([CH2:16][N+:17]#[C-])(=O)=O)=CC=1.[O:20]1[CH:24]=[CH:23][CH:22]=[C:21]1[C:25]1[O:26][C:27]([CH3:55])=[C:28]([CH2:30][O:31][C:32]2[CH:52]=[CH:51][C:35]([CH2:36][O:37][C:38]3[C:42]([CH:43]=O)=[CH:41][N:40]([C:45]4[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=4)[N:39]=3)=[CH:34][C:33]=2[O:53][CH3:54])[N:29]=1.O1CCCC1>C(COC)OC.O.CO>[O:20]1[CH:24]=[CH:23][CH:22]=[C:21]1[C:25]1[O:26][C:27]([CH3:55])=[C:28]([CH2:30][O:31][C:32]2[CH:52]=[CH:51][C:35]([CH2:36][O:37][C:38]3[C:42]([CH2:43][C:16]#[N:17])=[CH:41][N:40]([C:45]4[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=4)[N:39]=3)=[CH:34][C:33]=2[O:53][CH3:54])[N:29]=1

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 161915Tosylmethyl isocyanideHCID 23665647Potassium tert-butoxideHCID 866057753-[(4-{[2-(2-furyl)-5-methyl-1,3-oxazol-4-yl]methoxy}-3-methoxybenzyl)oxy]-1-phenyl-1H-pyrazole-4-carbaldehyde

Product 1

HCID 69216098{3-[(4-{[2-(2-furyl)-5-methyl-1,3-oxazol-4-yl]methoxy}-3-methoxybenzyl)oxy]-1-phenyl-1H-pyrazol-4-yl}acetonitrileYield 61%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent2×

Procedure

To a mixture of potassium tert-butoxide (0.94 g) and dimethoxyethane (30 mL) was added p-toluenesulfonyl methylisocyanide (0.86 g) at −78° C., and a solution of 3-[(4-{[2-(2-furyl)-5-methyl-1,3-oxazol-4-yl]methoxy}-3-methoxybenzyl)oxy]-1-phenyl-1H-pyrazole-4-carbaldehyde (1.96 g) in dimethoxyethane (50 mL)-tetrahydrofuran (10 mL) was added at −78° C. After stirring at the same temperature for 1 hr, the reaction mixture was heated to room temperature. Methanol (30 mL) was added to the obtained mixture, and the mixture was heated under reflux for 1 hr. After cooling, the reaction mixture was poured into water, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica gel column chromatography to give {3-[(4-{[2-(2-furyl)-5-methyl-1,3-oxazol-4-yl]methoxy}-3-methoxybenzyl)oxy]-1-phenyl-1H-pyrazol-4-yl}acetonitrile as colorless crystals (1.21 g, yield 61%) from a fraction eluted with ethyl acetate-hexane (1:1, v/v). Recrystallization from ethyl acetate-hexane gave colorless prism crystals. melting point: 153-154° C.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 1 hr
  3. temperatureAfter cooling
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe ethyl acetate layer was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-d08bc46de5bf413299a74ce29d69bfb4
Source dataset
uspto-grants-2008_05
Patent number
US07368578B2

Reaction notes

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