Sodium Carbonate → HCID 67674094, compound

Participants

Reaction Steps

To a solution of 830 g (1.50 Mol) (2R, 3S)-[2-[4-(tert-butyl-dimethyl-silanyloxy)-3-oxo-butyl]-1-(2,4-dimethoxy-benzyl)-4-oxo-azetidin-3-yl]-carbamic acid tert-butyl ester (4) in 8.3 l acetonitrile and 4.15 l water were added in intervals of 25 min three portions of 415 g (1.53 Mol) potassium persulfate at 72-75° C. The pH was kept at 4.9-5.3 by addition of a 10% solution of sodium carbonate (3.75 l). The mixture was stirred at the indicated temperature for 2 h and then cooled to room temperature. The solids were removed by filtration and washed with 5.6 l ethyl acetate. The filtrates were thoroughly mixed. The phases were separated and to the organic layer was added 2.54 l sodium bisulfite 40% in water. The phases were thoroughly mixed, cooled to 5-0° C., stirred for 1 h. The solids were removed by filtration and washed with 0.62 l ethyl acetate. The combined filtrates were stirred and the phases were allowed to separate. The organic phase was consecutively washed with aqueous solutions of 1.86 l sodium chloride (10%), 1.86 l sodium carbonate (5%) and twice with 1.86 l sodium chloride (10%), dried over 1.15 kg sodium sulfate and filtered. The solids were washed with 1.25 l ethyl acetate. To the combined filtrates was added 1.25 kg silica gel 60 (230-400 mesh) and the mixture was concentrated under aspirator vacuum. The remaining solid was charged onto a column containing 3.5 kg silica gel 60 (230-400 mesh). The product was eluted with a gradient of n-hexane:ethyl acetate=2:1 to 1:2. The pure product containing fractions were combined and concentrated under aspirator vacuum and dried 0,1 torr at 45° C. to yield 464 g (2R, 3S)-[2-[4-(tert-butyl dimethyl-silanyloxy)-3-oxo-butyl]-4-oxo-azetidin-3-yl]-carbamic acid tert-butyl ester (5) as a yellow amorphous solid (80% Th.).

Provenance & Evidence