Production of cephalosporins
AssigneeBristol-Myers Company
InventorsDerek Walker, Herbert H. Silvestri, Chester Sapino, David A. Johnson
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Abstract
In the preferred embodiment of the present invention trimethylsilyl 7-trimethylsilyloxycarbonylaminodecephalosporanate was prepared by bubbling dry carbon dioxide into an anhydrous solution of trimethylsilyl 6-trimethylsilylaminodecephalosporanate and found to be a useful intermediate in the production of cefadroxil and cephalexin by its acylation in anhydrous media with the appropriate 2-phenylglycyl chloride hydrochloride. Other cephalosporins are produced by acylation of 7-trimethylsilyloxycarbonylaminoceph-3-em-4-carboxylic acids or esters having a variety of substituents at the 3-position.
Claims20
A compound having the formula ##STR65## wherein B is --CH.sub.2 E;
- A is (CH.sub.3).sub.3 Si-- or an easily cleavable ester protecting group;
- and
- E is hydrogen or ##STR66##
A compound having the formula ##STR67## wherein A is (CH.sub.3).sub.3 Si-- and
- E is hydrogen or ##STR68##
A compound having the formula ##STR69## wherein A is an easily cleavable ester protecting group;
- and
- E is hydrogen or ##STR70##
The compound having the formula ##STR76## wherein A is (CH.sub.3).sub.3 Si-- and
- E is hydrogen.
The compound having the formula ##STR77## wherein A is (CH.sub.3).sub.3 Si-- and
- E is ##STR78##
The process for the production of a compound of the formula ##STR79## wherein B is --CH.sub.2 E;
- A is (CH.sub.3).sub.3 Si-- or an easily cleavable ester protecting group;
- and
- E is hydrogen or ##STR80## which comprises adding dry carbon dioxide to a solution of a compound having the formula ##STR81## wherein A and B have the same meaning as above in an anhydrous inert organic solvent at a temperature in the range of 0.degree. C. to 100.degree. C. until completion of the reaction.
In the process for the production of a conventional cephalosporin having the formula ##STR93## wherein ##STR94## is the residue after removal of the hydroxyl group of an organic carboxylic acid containing from two to twenty carbon atoms, and B is --CH.sub.2 E wherein
- E is hydrogen or ##STR95## which comprises the consecutive steps of acylating with the acid chloride of said organic carboxylic acid a silylated nucleus having the formula ##STR96## wherein A is (CH.sub.3).sub.3 Si-- or an easily cleavable ester protecting group and B has the same meaning as above and then converting group A to hydrogen,
- the improvement which comprises, prior to acylation, converting said silylated nucleus to a compound of the formula ##STR97## wherein A and B have the same meaning as above, by adding dry carbon dioxide to a solution of said silylated nucleus in an anhydrous inert organic solvent at a temperature in the range of 0.degree. C. to 100.degree. C. until completion of the carbonylation reaction.
In the process of claim 26 for the production of a conventional cephalosporin having the formula ##STR98## wherein ##STR99## is the residue removal of the hydroxyl group of an organic carboxylic acid containing from two to twenty carbon atoms, and
- E is hydrogen or ##STR100## which comprises the consecutive steps of acylating with the acid chloride of said organic carboxylic acid a silylated nucleus having the formula ##STR101## wherein A is (CH.sub.3).sub.3 Si, and
- E has the same meaning as above and then converting group A to hydrogen,
- the improvement which comprises, prior to acylation, converting said silylated nucleus to a compound of the formula ##STR102## wherein A and E have the same meaning as above, by adding dry carbon dioxide to a solution of said silylated nucleus in an anhydrous inert organic solvent at a temperature in the range of 0.degree. C. to 100.degree. C. until completion of the carbonylation reaction.
Dependencies are inferred from the claim text.