反应详情

A stirred mixture of 4.40 g of 5,6-dimethoxy-3-(4-piperidyl-1,2-benzisoxazole, 3.35 g of 1-(3-chloropropyl)-1,3-dihydro-2H-benzimidazole-2-one, 3.56 g of sodium carbonate, 300 ml of 4-methyl-2-pentanone and 0.20 g of potassium iodide was stirred at reflux for 6.0 hrs and stirred overnight at ambient temperature. The reaction mixture was poured into water (300 ml) and extracted with dichloromethane. The extract was dried over anhydrous magnesium sulfate and the solvent was removed in vacuo to yield an oil. The oil was purified by high pressure liquid chromatography (Waters Prep 500; two silica gel columns) using 5% methanol in dichloromethane as the eluent. The free base was dissolved in ether and a saturated hydrogen bromide/ether solution was added dropwise to precipitate the hydrobromide salt. The salt was filtered, washed with ether and recrystallized from toluene/ether to yield 2.50 g (28.1%) of the product, mp 147°-149°.

1. temperatureat reflux for 6.0 hrs
2. stirringstirred overnight at ambient temperature
3. extractionextracted with dichloromethane
4. dry with materialThe extract was dried over anhydrous magnesium sulfate
5. customthe solvent was removed in vacuo
6. customto yield an oil
7. customThe oil was purified by high pressure liquid chromatography (Waters Prep 500; two silica gel columns)
8. dissolutionThe free base was dissolved in ether
9. additiona saturated hydrogen bromide/ether solution was added dropwise
10. customto precipitate the hydrobromide salt
11. filtrationThe salt was filtered
12. washwashed with ether
13. customrecrystallized from toluene/ether