反应详情

N-[3-(Quinolin-7-yloxy)propyl]-2,3-dihydro-7-methoxy-1,4-benzodioxin-2-methanamine dihydrochloride monohydrate (0.94 g, 2.0 mmole), prepared above in Example 4, was dissolved in 10 ml of 48% HBr and refluxed for 24 hours under a nitrogen atmosphere. Upon cooling, the mixture was poured into 100 ml of saturated sodium bicarbonate solution to which 50 g of ice had been added. When the ice had melted, the mixture was extracted three times with 150 ml portions of 3:1 dichloromethane-isopropanol, the extracts dried over sodium sulfate, filtered, and concentrated in vacuum. The residue was column chromatographed on 50 g of silica gel with 3% methanol/chloroform and the product-containing fractions were combined and concentrated in vacuum. The crude free base thus obtained was crystallized from 50 ml of ethanol with the addition of 3 ml of 4N isopropanolic HCl to give 0.5 g of the title compound as a yellow dihydrochloride monohydrate, m.p. 245°-246° C.

1. temperaturerefluxed for 24 hours under a nitrogen atmosphere
2. temperatureUpon cooling
3. additionhad been added
4. extractionthe mixture was extracted three times with 150 ml portions of 3:1 dichloromethane-isopropanol
5. dry with materialthe extracts dried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuum
8. customchromatographed on 50 g of silica gel with 3% methanol/chloroform
9. concentrationconcentrated in vacuum
10. customThe crude free base thus obtained
11. customwas crystallized from 50 ml of ethanol with the addition of 3 ml of 4N isopropanolic HCl