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

Participants

Reaction Steps

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.

Provenance & Evidence