反应详情

温度

-10 °C

The compound 5 DCM solution was transferred into a clean reactor and cooled to −13 to −7° C. Dichloromethane (6 volumes) was charged and followed by aluminum chloride (1.03 eq) while maintaining the temperature at not more than −7° C. Acetyl chloride (1.12 eq) was slowly charged to the mixture while maintaining the temperature at not more than −10° C. The reaction mixture was agitated at −13 to −7° C. and the progress of the acylation reaction was monitored by HPLC. After the acylation was completed the reaction mixture was transferred onto 5 volumes of cold (2 to 8° C.) water while maintaining the temperature at not more than 25° C. The quenched mixture was allowed to warm to 19 to 25° C. and agitated till a biphasic mixture was formed. The organic phase was separated and washed with water (3 volumes). The organic phase was separated and concentrated by vacuum distillation. The solvent was exchanged to 2-propanol by coevaporation under vacuum. The slurry formed was diluted with 2-propanol (1 volume) and then heated to reflux to form a solution. Heptane (2.9 volumes) was slowly charged to the hot solution and cooled to 0 to 5° C. to form a slurry. The product was isolated by filtration. The wet cake was washed with a mixture of 2-propanol and heptane and dried at not more than 40° C. to yield approximately 75% of compound 8 as an off-white to light pink solid. 1H NMR (CDCl3) δ 7.66 (s, 1H), 7.18 (td, 1H, J=7 Hz, 2 Hz), 6.88-6.98 (m, 2H), 6.42 (s, 1H), 3.89-3.92 (m, 5H), 3.85 (s, 3H), 2.55 (s, 3H).

1. temperaturewhile maintaining the temperature at not more than −7° C
2. temperaturewhile maintaining the temperature at not more than −10° C
3. customthe progress of the acylation reaction
4. temperaturewhile maintaining the temperature at not more than 25° C
5. temperatureto warm to 19 to 25° C.
6. stirringagitated till a biphasic mixture
7. customwas formed
8. customThe organic phase was separated
9. washwashed with water (3 volumes)
10. customThe organic phase was separated
11. concentrationconcentrated by vacuum distillation
12. customThe slurry formed
13. temperatureheated
14. temperatureto reflux
15. customto form a solution
16. temperaturecooled to 0 to 5° C.
17. customto form a slurry
18. customThe product was isolated by filtration
19. washThe wet cake was washed with a mixture of 2-propanol and heptane
20. customdried at not more than 40° C.