Chlorotrimethylsilane → 3-Carbamoyloxymethyl-7-amino-3-cephem-4-carboxylic acid

Participants

Reaction Steps

To a stirred slurry of 3.0 grams of 7-(5-phthalimido-5-carboxyvaleramido)-3-carbamoyloxymethyl-3-cephem-4-carboxylic acid in 50 milliliters of absolute methylene chloride were added 2.9 milliliters of absolute pyridine and 4.5 milliliters of trimethylchlorosilane, to protect both of the carboxyl groups. The resulting reaction mixture was stirred for two and one-half hours, then cooled to -12° C. in a carbon tetrachloride: dry ice bath. To this were added 5.6 milliliters of absolute pyridine in one lot, and then 36.2 milliliters of a 10 percent solution of phosphorus pentachloride in absolute methylene chloride, dropwise, maintaining the temperature at -12° C. The reaction mixture was stirred for two and one-half hours, 40 milliliters of absolute methanol was added dropwise at -12° C. and stirred for thirty minutes, and for another thirty minutes at room temperature. Then 10 milliliters of 50 percent formic acid was added dropwise, the pH adjusted to 2 by addition of triethylamine, and the reaction mixture stirred for forty-five minutes. The solution became cloudy. Then the pH was adjusted to 3.4, and the reaction mixture was refrigerated overnight and filtered, yielding 600 milligrams of 7-amino-3-carbamoyloxymethyl-3-cephem-4-carboxylic acid, 40 percent yield. This was taken up in 5 milliliters of water, stirred and filtered. The solid was washed with about 2 milliliters of water and 10 milliliters of acetone, yielding 450 milligrams of purified 7-amino-3-carbamoyloxymethyl-3-cephem-4-carboxylic acid, 30 percent yield.

Provenance & Evidence