Sodium Hydroxide → HCID 13239640, compound

Participants

Reaction Steps

A total of 12.76 g (30 mmoles) of (6R,7R)-7-amino-3-(1-methyl-1-pyrrolidinio)methylceph-3-em-4-carboxylate monohydroiodide (prepared in Example 19) was suspended in 87 ml of water with good stirring at 20°-25° C. The slurry was cooled to 8°-10° C., and the pH was raised to 5.80 at 7° C. by dropwise addition of 13.0 ml (26 mmoles, 0.87 equivalents) of 2N sodium hydroxide solution over a period of 35 minutes. Next, 555 ml of tetrahydrofuran was added, and the pH of the resulting solution was increased to 6.8 at 10° C. by dropwise addition of 1.9 ml (3.8 mmoles, 0.13 equivalents) of 2N sodium hydroxide solution. The cooling bath was removed, and 29.5 g (92.7 mmoles, 1.5 equivalents) of the HOBT active ester of syn-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetic acid was added in two equal portions of 14.75 g each over 30 minutes. Following each addition, the pH was readjusted to 6.5 every 5-10 minutes, by dropwise addition of 2N sodium hydroxide solution. In the remaining reaction time, the pH was readjusted to 6.5 by dropwise addition of 2N sodium hydroxide solution every 15 minutes (total 2N sodium hydroxide used was 28.6 ml (57.2 mmoles, 1.91 equivalents).

Provenance & Evidence