Acetyl chloride → HCID 86691271, compound

Participants

Reaction Steps

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).

Provenance & Evidence