反应详情

A mixture of 1-(2-chloroethyl)isochroman (LXIV, PREPARATION 2, 0.497 g, 2.53 mmol), 1-(2-chlorophenyl)piperazine dihydrochloride (XI, 0.952 g, 3.79 mmol), diisopropylethylamine (1.76 ml, 10.1 mmol) and ethylene glycol (5 ml) is heated at 100° for 16 hr. After cooling, the mixture is partitioned between ethyl acetate and saline. The organic phase is dried over magnesium sulfate, concentrated, and the residue chromatographed on silica gel eluting with methanol/dichloromethane (2/98) to give a material which is taken up in several mls of methanol. Methanol saturated with hydrochloric gas (6 ml) is added. After standing for several minutes, the mixture is concentrated under reduced pressure. Several mls of methanol are added back, followed by ether. The resulting solid is collected, washed with ether, and dried under vacuum to give the title compound; mp 197°-198°; MS ((m/z)) 356; IR (mineral oil) 1093, 1481, 743, 2436 and 2426 cm-1.

1. temperatureis heated at 100° for 16 hr
2. temperatureAfter cooling
3. customthe mixture is partitioned between ethyl acetate and saline
4. dry with materialThe organic phase is dried over magnesium sulfate
5. concentrationconcentrated
6. customthe residue chromatographed on silica gel eluting with methanol/dichloromethane (2/98)
7. customto give a material which
8. waitAfter standing for several minutes
9. concentrationthe mixture is concentrated under reduced pressure
10. additionSeveral mls of methanol are added back
11. customThe resulting solid is collected
12. washwashed with ether
13. customdried under vacuum