Hydrochloric Acid → acetyloxymethyl (6R,7R)-3-(carbamoyloxymethyl)-7-[[(2Z)-2-(furan-2-yl)-2-methoxyiminoacetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

Participants

Reaction Steps

A solution (6R,7R)-3-carbamoyloxymethyl-7-[(Z)-2-(fur-2-yl)-2-methoxyiminoacetamido]ceph-3-em-4-carboxylic acid (12.00 g) in N,N-dimethylformamide (70 ml) was stirred for 10 minutes with potassium carbonate (1.95 g), during which time the mixture became darker and the solid almost completely dissolved. A solution of acetoxymethyl bromide (5.0 g) in N,N-dimethylformamide (15 ml) was then added, whereupon precipitation of potassium bromide occurred almost immediately. The reaction mixture was stirred at 21° for 30 minutes, after which it is shown by t.l.c. (developing with chloroform:acetone=2:1 and observing the spots under u.v. light and by spraying with ninhydrin and heating to 120°) to contain no unreacted cephalosporin starting material. The reaction mixture was then poured into a mixture of 2 N-hydrochloric acid (350 ml) and ethyl acetate (350 ml), and the aqueous phase was extracted with further ethyl acetate (2×200 ml). The organic extracts were combined and were washed successively with 2 N-hydrochloric acid (2× 300 ml), water (2×300 ml), aqueous sodium bicarbonate solution (3%, 300 ml), water (3×300 ml), and saturated sodium chloride solution (2×300 ml), and dried (MgSO4), and the solvent was removed in vacuo to give a yellow froth (13.87 g). This product was absorbed onto a column of silica gel (Hopkin and Williams, 100 to 200 mesh-330 g) which was eluted with chloroform:acetone=2:1; 25 ml fractions were collected. Evaporation of fractions 11 to 32 gave crude title ester, which crystallised during the evaporation. The resulting solid (7.217 g) was triturated with ether to give the title ester (6.58 g) as a white powder, m.p. 181° to 183° (Kofler); [α]D +58° (c 0.98, DMSO), [α]D +72° (c 1.32, dioxan); λmax (EtOH) 276 nm (ε 19,750). The nmr and infrared data are shown in Table 1 hereinafter. The structure of the product was also confirmed by microanalysis.

Provenance & Evidence