Acetyl chloride → HCID 86691271、化合物

Under a nitrogen atmosphere, add acetyl chloride (86.5 mL, 1.2 mol) to absolute ethanol (1.0 L, 17.2 mol) drop-wise while maintaining the internal reaction temperature below 30° C. Stir the resulting mixture for 15 minutes and add di-t-butyl (1S,2S,5R,6R)-2-(tert-butoxycarbonylamino)-4-oxo-bicyclo[3.1.0]hexane-2,6-dicarboxylate (100 g, 0.24 mol) in one portion. Heat the resulting mixture to reflux for 16-20 hours. Concentrate the reaction mixture to an oil under reduced pressure. Dissolve the crude product in methylene chloride (250 mL) and concentrate in vacuo. Repeat the methylene chloride/concentration process to afford a white foam. Add ethyl acetate (150 mL) and heat the mixture to 65° C. Add methyl t-butyl ether (100 mL) and stir the mixture at 65° C. for 15 minutes. Add methyl t-butyl ether (300 mL) over 15 minutes, stir at 65° C. for 15 minutes, then shut heat and allow the slurry to cool to ambient temperature. Filter the mixture and wash the filter cake with methyl t-butyl ether (150 mL). Transfer the cake to a vacuum oven and dry overnight at 25° C. to afford the crude product (67.5 g). Transfer the solids to a round bottom flask, dilute with ethyl acetate (170 mL) and heat the mixture to 65° C. Stir the mixture for 1 hour, add tetrahydrofuran (68 mL) and ethanol (3 mL). Shut heat source and add methyl t-butyl ether (272 mL) over 20 minutes, allowing the mixture to cool to ambient temperature. Filter the slurry, wash the cake with 95/5 methyl t-butyl ether/ethyl acetate (2×75 mL) and further dry the solids in a vacuum oven overnight at 25° C. to afford the title compound as a white solid (60.0 g, 98.0%). MS (m/z): 256 (M+1).

1. temperaturewhile maintaining the internal reaction temperature below 30° C
2. temperatureHeat the resulting mixture
3. temperatureto reflux for 16-20 hours
4. concentrationConcentrate the reaction mixture to an oil under reduced pressure
5. dissolutionDissolve the crude product in methylene chloride (250 mL)
6. concentrationconcentrate in vacuo
7. concentrationRepeat the methylene chloride/concentration process
8. customto afford a white foam
9. stirringstir at 65° C. for 15 minutes
10. temperatureshut heat
11. filtrationFilter the mixture
12. washwash the filter cake with methyl t-butyl ether (150 mL)
13. customTransfer the cake to a vacuum oven and dry overnight at 25° C.
14. customto afford the crude product (67.5 g)
15. temperatureheat the mixture to 65° C
16. stirringStir the mixture for 1 hour
17. temperatureShut heat source
18. temperatureto cool to ambient temperature
19. filtrationFilter the slurry
20. washwash the cake with 95/5 methyl t-butyl ether/ethyl acetate (2×75 mL)
21. customfurther dry the solids in a vacuum oven overnight at 25° C.

ORDレコード

ord-83637cfe2f9b464c8a0a84bbc0d1e796

出典データセット

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08575214B2