反应详情

温度

1 °C

Cool a solution of the ethyl 2-methyl-2-phenoxypropanoate, (1.0wt, 1.0eq), in dichloromethane (7.5vols) to 0° C. with stirring under a nitrogen atmosphere. Slowly add neat chlorosulfonic acid (0.78wt, 1.4eq) to the reaction mixture at a rate such that the reaction temperature never rises above 5.0° C. The addition typically takes 30minutes to complete. Following the completion of the addition, stir the reaction mixture at 0-1° C. Follow the course of the reaction by HPLC. The reaction is typically complete after 30minutes. At this point, slowly treat the reaction mixture with DMF (1.75L) (1.40wt, 4.0eq). The addition of DMF to the reaction mixture is very exothermic. Adjust the rate of addition so that the reaction temperature never rises above 10.0° C. The addition of DMF to the reaction mixture takes approximately 30minutes. Following the completion of the DMF addition, re-cool the reaction mixture to 0.5to 1° C. Treat the cooled reaction mixture with neat thionyl chloride (619mL, 1.01kg) (0.86wt, 1.5eq). Adjust the rate of addition so that the process temperature never reaches 5° C. The addition of thionyl chloride to the reaction mixture is not very exothermic at all. Hence, the addition of thionyl chloride is typically complete in 5minutes. Following the completion of the DMF addition, warm the reaction mixture to 20° C. with stirring. Follow the course of the reaction via HPLC. After 2.0h, the reaction is typically complete. At this point, cool the reaction mixture to 0-1° C. and carefully treat the reaction mixture with water (8.8L) (7.5vols). [Note: The addition of water may be somewhat exothermic depending upon how much unreacted thionyl chloride is left in the reaction mixture.] Separate the organic layer and wash the organic layer with aqueous 0.1N HCl solution (2×7.5vols). Separate the organic layer, concentrate the organic layer to a minimum stir volume, treat the organic layer with isopropyl acetate (1×5.0vols) and then concentrate the resulting solution via vacuum distillation to afford the titled compound as a translucent bronze colored oil.

1. customsuch that the reaction temperature never rises above 5.0° C
2. additionThe addition typically takes 30minutes
3. additionthe completion of the addition
4. stirringstir the reaction mixture at 0-1° C
5. customthe course of the reaction by HPLC
6. additionthe rate of addition so that the reaction temperature never rises above 10.0° C
7. waittakes approximately 30minutes
8. additionTreat
9. additionthe rate of addition so that the process temperature never reaches 5° C
10. waitis typically complete in 5minutes
11. temperaturewarm the reaction mixture to 20° C.
12. stirringwith stirring
13. customthe course of the reaction via HPLC
14. temperatureAt this point, cool the reaction mixture to 0-1° C.
15. waitis left in the reaction mixture
16. custom] Separate the organic layer
17. washwash the organic layer with aqueous 0.1N HCl solution (2×7.5vols)
18. customSeparate the organic layer
19. concentrationconcentrate the organic layer to a minimum stir volume
20. additiontreat the organic layer with isopropyl acetate (1×5.0vols)
21. concentrationconcentrate the resulting solution
22. distillationvia vacuum distillation