反应详情

Methyl {8-fluoro-2-[4-(3-methoxyphenyl)piperazin-1-yl]-3-[2-methoxy-5-(trifluoromethyl)-phenyl]-3,4-dihydroquinazolin-4-yl}acetate (64 g) is dissolved in 1,4-dioxane (450 ml) and 1N sodium hydroxide solution (325 ml) and stirred at room temperature for 2 h, then some of the solvent is distilled off at 30° C. in vacuo (400 ml). Subsequently, toluene (300 ml) is added and the phases are separated. The aqueous phase is washed with toluene (twice 150 ml), then the combined organic phases are extracted again with 1N sodium hydroxide solution (50 ml). The pH of the combined aqueous phases is adjusted to 7.5 with 2N hydrochloric acid (ca. 150 ml), then MIBK (150 ml) is added. The phases are separated, the aqueous phases are extracted again with MIBK (150 ml), then the combined MIBK phases are dried over sodium sulphate and concentrated at 45° C. A total of 64 g of (±)-{8-fluoro-2-[4-(3-methoxyphenyl)piperazin-1-yl]-3-(2-methoxy-5-trifluoromethylphenyl)-3,4-dihydroquinazolin-4-yl}acetic acid are obtained in quantitative yield as an amorphous solid.

1. distillationsome of the solvent is distilled off at 30° C. in vacuo (400 ml)
2. additionSubsequently, toluene (300 ml) is added
3. customthe phases are separated
4. washThe aqueous phase is washed with toluene (twice 150 ml)
5. extractionthe combined organic phases are extracted again with 1N sodium hydroxide solution (50 ml)
6. additionMIBK (150 ml) is added
7. customThe phases are separated
8. extractionthe aqueous phases are extracted again with MIBK (150 ml)
9. dry with materialthe combined MIBK phases are dried over sodium sulphate
10. concentrationconcentrated at 45° C