反应详情

(±)-{8-Fluoro-2-[4-(3-methoxyphenyl)piperazin-1-yl]-3-(2-methoxy-5-trifluoromethylphenyl)-3,4-dihydroquinazolin-4-yl}acetic acid (54 g) is dissolved in methanol (540 g), then concentrated sulphuric acid (7.85 ml) is added. The mixture is stirred under reflux for 26 h, then cooled and concentrated in vacuo to ca. one third of the original volume. Water (150 ml) and dichloromethane (150 ml) are added, then the phases are separated. The organic phase is extracted with saturated sodium hydrogencarbonate solution (two times 140 ml), dried over sodium sulphate and concentrated to give a foamy residue. This is dissolved twice in succession in ethanol (150 ml each) and concentrated, and subsequently dried for 18 h in vacuo using entraining nitrogen. A total of 41.6 g of methyl {8-fluoro-2-[4-(3-methoxyphenyl)piperazin-1-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl}acetate are thus obtained as an amorphous solid, corresponding to 75.2% of theory.

1. temperatureunder reflux for 26 h
2. temperaturecooled
3. concentrationconcentrated in vacuo
4. additionWater (150 ml) and dichloromethane (150 ml) are added
5. customthe phases are separated
6. extractionThe organic phase is extracted with saturated sodium hydrogencarbonate solution (two times 140 ml)
7. dry with materialdried over sodium sulphate
8. concentrationconcentrated
9. customto give a foamy residue
10. concentrationconcentrated
11. customsubsequently dried for 18 h in vacuo