Sodium hydride → 5-[4-(6-Chloro-2-pyridinyloxy)-phenoxymethyl]3-cyclopropylisoxazole

HRID 36621Notes

Reaction equation

HRID 36621 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=2)[CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[H][H].Cl[CH2:21][C:22]1[O:26][N:25]=[C:24]([CH:27]2[CH2:29][CH2:28]2)[CH:23]=1>CN(C)C=O>[Cl:1][C:2]1[N:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:21][C:22]3[O:26][N:25]=[C:24]([CH:27]4[CH2:29][CH2:28]4)[CH:23]=3)=[CH:11][CH:10]=2)[CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 146501055-(Chloromethyl)-3-cyclopropyl-1,2-oxazoleHCID 146736064-(6-Chloro-2-pyridinyloxy)phenolHCID 178418361HCID 178418361, compound

Product 1

HCID 146736175-[4-(6-Chloro-2-pyridinyloxy)-phenoxymethyl]3-cyclopropylisoxazoleYield 78.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
50 °C

Procedure

At room temperature (about 20° C.), 11.1 g of 4-(6-chloro-2-pyridinyloxy)-phenol in 100 ml of anhydrous dimethylformamide is dripped into 1.3 g of 100% strength sodium hydride in 40 ml of anhydrous dimethylformamide. To complete the exothermic reaction (evolution of hydrogen) the mixture is stirred for 30 minutes at 50° C. At room temperature, 7.9 g of 5-chloromethyl-3-cyclopropylisoxazole in 30 ml of anhydrous dimethylformamide is then dripped in. The mixture is stirred for 2 hours at 60° C. and overnight at room temperature. It is then poured into 200 ml of ice water and the solution is extracted with methyl tert-butyl ether. The organic phase is then washed with sodium hydroxide solution, water and saturated sodium chloride solution. After drying over sodium sulfate, the solvent is evaporated under reduced pressure. The crude product is recrystallized from methanol. There is obtained 13.5 g of 5-[4-(6-chloro-2-pyridinyloxy)-phenoxymethyl]3-cyclopropylisoxazole of m.p.: 128°-130° C.

Workup

  1. customAt room temperature
  2. customAt room temperature
  3. stirringThe mixture is stirred for 2 hours at 60° C. and overnight at room temperature
  4. extractionthe solution is extracted with methyl tert-butyl ether
  5. washThe organic phase is then washed with sodium hydroxide solution, water and saturated sodium chloride solution
  6. dry with materialAfter drying over sodium sulfate
  7. customthe solvent is evaporated under reduced pressure
  8. customThe crude product is recrystallized from methanol

Sources & evidence

ORD record
ord-594e35d494214bbe8c9434c4943775b2
Source dataset
uspto-grants-1995_05
Patent number
US05416100

Reaction notes

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