反应详情

温度

64 °C

A 2 l, 4-necked glass reactor equipped with a mechanical stirrer, a thermometer, a cooler, a dropping funnel and an argon inlet was charged under argon in sequence with 103.2 g (250 mmol) of tributylammonium hydroxy-(4-hydroxy-benzo[b]thiophen-7-yl)-acetate, 151.3 g (287 mmol) of iron(III) sulfate, 150 ml of isopropanol, a mixture of 750 ml of water and 150 ml of 2 N sulfuric acid. The reaction mixture was heated under stirring to 63-65° C. for 2 h. After cooling to room temperature, 600 ml of isopropyl acetate were added and the mixture filtered. The filtrate was washed with 100 ml of water, then the organic phase was concentrated (ca. 470 ml were distilled off at 50° C./150-50 mbar). After addition of 625 ml of DMF, the rest of more volatile solvents are removed completely at 50° C./150-50 mbar. The water content at this point was less than 0.4%. This suspension containing the intermediate 4-hydroxy-benzo[b]thiophene-7-carboxaldehyde was transferred with aid of 660 ml of DMF in a 4 l reactor (equipped as the 2 l reactor above) which had been charged with 38.0 g of potassium carbonate. To the dark suspension was added within 60 min at 86-90° C. a solution of 70.4 g (250 mmol) of 2-(5-methyl-2-phenyl)-4-oxazolyl)ethanol methanesulfonyl ester in 275 ml of DMF. The reaction mixture was stirred at the same temperature for 6 h, then 450 ml of toluene followed by 950 ml of water were added, whereas the temperature was kept above 75° C. The aqueous phase was separated and extracted with 150 ml of warm toluene. The two toluene phases were combined, re-extracted with water and finally treated at a temperature between 65 and 40° C. with 900 ml of methanol. The resulting suspension was stirred for 1 h at 40° C., cooled to −15° C. and stirred for 3 h at −15° C. Finally the suspension was filtered, the filter cake was washed with 100 ml of a cold (−15° C.) toluene/methanol mixture and dried at 60° C./10 mbar to afford 76.8 g (84.5%) of 4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxyl]-benzo[b]thiophene-7-carbaldehyde as colorless crystals with a m.p. of 154° C.

1. customA 2 l, 4-necked glass reactor equipped with a mechanical stirrer
2. temperatureThe reaction mixture was heated
3. temperatureAfter cooling to room temperature
4. filtrationthe mixture filtered
5. washThe filtrate was washed with 100 ml of water
6. concentrationthe organic phase was concentrated
7. distillation(ca. 470 ml were distilled off at 50° C./150-50 mbar)
8. additionAfter addition of 625 ml of DMF
9. customthe rest of more volatile solvents are removed completely at 50° C./150-50 mbar
10. additionThis suspension containing the intermediate 4-hydroxy-benzo[b]thiophene-7-carboxaldehyde
11. customwas transferred with aid of 660 ml of DMF in a 4 l reactor
12. custom(equipped as the 2 l reactor above) which
13. additionhad been charged with 38.0 g of potassium carbonate
14. stirringThe reaction mixture was stirred at the same temperature for 6 h
15. additionwere added, whereas the temperature
16. customwas kept above 75° C
17. customThe aqueous phase was separated
18. extractionextracted with 150 ml of warm toluene
19. extractionre-extracted with water
20. additionfinally treated at a temperature between 65 and 40° C. with 900 ml of methanol
21. stirringThe resulting suspension was stirred for 1 h at 40° C.
22. temperaturecooled to −15° C.
23. stirringstirred for 3 h at −15° C
24. filtrationFinally the suspension was filtered
25. washthe filter cake was washed with 100 ml of a cold (−15° C.) toluene/methanol mixture
26. customdried at 60° C./10 mbar