Phosphorus oxychloride → 7-[2-Propoxyimino-2-(2-aminothiazol-4-yl)acetamido]-3-(1-pyridiniomethyl)-3-cephem-4-carboxylate

Participants

Reaction Steps

Phosphorus oxychloride (1.7 g) was added to a stirred suspension of 2-propoxyimino-2-(2-aminothiazol-4-yl)acetic acid (syn isomer) (2.0 g) in dry tetrahydrofuran (20 ml) and water (0.114 g) at 0° to 3° C. and the resulting mixture was stirred for 30 minutes and thereto was added N-trimethylsilylacetamide (1.2 g) at the same temperature. The resulting mixture was stirred for 15 minutes and thereto was added phosphorus oxychloride (1.7 g) at the same temperature and then stirred for 15 minutes. To the resulting mixture was added dry N,N-dimethylformamide (0.9 g) at the same temperature and then stirred for 30 minutes [Solution A]. N-trimethylsilylacetamide (11.4 g) was added to a stirred suspension of 1-[(7-amino-4-carboxy-3-cephem-3-yl)methyl]pyridinium chloride hydrochloride dihydrate (3.5 g) in tetrahydrofuran (70 ml). To the resulting solution was dropwise added the Solution A at -5° C. and stirred at 0° to -5° C. for 40 minutes. To the reaction mixture was added water and ethyl acetate at -5° C. The aqueous layer was separated, washed with ethyl acetate and then adjusted to pH 4.0 with 10% aqueous solution of sodium hydroxide under ice-cooling. The solution was subjected to column chromatography on macroporous non-ionic adsorption resin "Diaion HP-20" (Trademark: Prepared by Mitsubishi Chemical Industries) and eluted with 20% aqueous solution of isopropyl alcohol. The fractions containing the object compound were collected, concentrated and lyophilized to give 7-[2-propoxyimino-2-(2-aminothiazol-4-yl)acetamido]-3-(1-pyridiniomethyl)-3-cephem-4-carboxylate (syn isomer).

Provenance & Evidence