Imidazole → 5-Chloro-3-(imidazol-1-ylmethyl)-1,2-benzoxazole

HRID 1723070Notes

Reaction equation

HRID 1723070 reaction equation
[H-].[Na+].[NH:3]1[CH:7]=[CH:6][N:5]=[CH:4]1.[Cl:8][C:9]1[CH:10]=[CH:11][C:12]2[O:16][N:15]=[C:14]([CH2:17]Br)[C:13]=2[CH:19]=1>CN(C)C=O>[Cl:8][C:9]1[CH:10]=[CH:11][C:12]2[O:16][N:15]=[C:14]([CH2:17][N:3]3[CH:7]=[CH:6][N:5]=[CH:4]3)[C:13]=2[CH:19]=1

Participants

5

Reactant 3

HCID 795ImidazoleHCID 24758Sodium hydrideHCID 14575000HCID 14575000, compound

Product 1

HCID 1865935-Chloro-3-(imidazol-1-ylmethyl)-1,2-benzoxazole

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Sodium hydride (60% in mineral oil, 276.6 g, 6.92 moles) is added in portions to a solution of imidazole (471 g, 6.92 moles) in dimethylformamide (4 L) over a period of 1 hour. After the addition is complete, the resulting suspension is stirred for 1 hour at ambient temperature. A solution of 5-chloro-3-bromomethyl-1,2-benzisoxazole (1.57 kg, 6.37 moles) in dimethylformamide (3 L) is then added over a period of 30 minutes, during which time there is an exotherm from 24° C. to 68° C. On completion of this addition, the reaction mixture is stirred and heated at 90° C. for 2 hours. The solvent is then removed in vacuo and the residue is taken up in methylene chloride (4 L). The resulting suspension is washed with water (2×2 L), which dissolves the solid material, and the organic solution is then dried over anhydrous sodium sulfate (1 kg), filtered and evaporated to give 5-chloro-3-[(1H-imidazol-1-yl)methyl]-1,2-benzisoxazole, m.p. 100°-102° C.; hydrochloride salt, m.p. 201°-203° C.

Workup

  1. additionAfter the addition
  2. customfrom 24° C. to 68° C
  3. additionOn completion of this addition
  4. stirringthe reaction mixture is stirred
  5. temperatureheated at 90° C. for 2 hours
  6. customThe solvent is then removed in vacuo
  7. washThe resulting suspension is washed with water (2×2 L), which
  8. dissolutiondissolves the solid material
  9. dry with materialthe organic solution is then dried over anhydrous sodium sulfate (1 kg)
  10. filtrationfiltered
  11. customevaporated

Sources & evidence

ORD record
ord-8a2129a649b3433a8ddb461af4241a07
Source dataset
uspto-grants-1989_08
Patent number
US04859691

Reaction notes

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