Described herein are crystalline forms of a compound of formula (III), including toluene solvates of TATD-CLE, as well as processes for the preparation thereof and use thereof in the preparation of cephalosporin compounds such as ceftolozane.

Described herein are crystalline forms of a compound of formula (III), including toluene solvates of TATD-CLE, as well as processes for the preparation thereof and use thereof in the preparation of cephalosporin compounds such as ceftolozane.

This disclosure provides methods of making certain 7-aminocephem derivatives useful in the manufacture of cephalosporin antibiotic compounds.

This disclosure provides methods of making certain 7-aminocephem derivatives useful in the manufacture of cephalosporin antibiotic compounds.

Described herein are crystalline forms of a compound of formula (II), including toluene solvates off A TD-CLE, as well as processes for the preparation thereof and use thereof in the preparation of cephalosporin compounds such as ceftolozane. Provided herein is a crystalline form of a compound of formula (II): wherein X is CI, Br, or I; and R1 and R2 are each independently an oxygen protecting group; processes for making the crystalline form, and use of said form in the synthesis of antibacterial cephalosporins such as ceftolozane.

Described herein are crystalline forms of a compound of formula (II), including toluene solvates off A TD-CLE, as well as processes for the preparation thereof and use thereof in the preparation of cephalosporin compounds such as ceftolozane. Provided herein is a crystalline form of a compound of formula (II): wherein X is CI, Br, or I; and R1 and R2 are each independently an oxygen protecting group; processes for making the crystalline form, and use of said form in the synthesis of antibacterial cephalosporins such as ceftolozane.

A synthesis process of precursors of derivatives of beta-lactam compounds, said beta-lactam compounds being selected from 6-aminopenicillanic acid and 7-aminocephalosporanic acid, preferably 6-aminopenicillanic acid, comprising the following steps: a) protection of the amine group of the beta-lactam compound, selected from 6-aminopenicillanic acid and 7-aminocephalosporanic acid, preferably 6-aminopenicillanic acid, through the formation of a carbamate by reaction with a dicarbonate; b) esterification of the carboxyl group in position 2 of the beta-lactam compound obtained in step a) by reaction with propargyl alcohol.

A synthesis process of precursors of derivatives of beta-lactam compounds, said beta-lactam compounds being selected from 6-aminopenicillanic acid and 7-aminocephalosporanic acid, preferably 6-aminopenicillanic acid, comprising the following steps: a) protection of the amine group of the beta-lactam compound, selected from 6-aminopenicillanic acid and 7-aminocephalosporanic acid, preferably 6-aminopenicillanic acid, through the formation of a carbamate by reaction with a dicarbonate; b) esterification of the carboxyl group in position 2 of the beta-lactam compound obtained in step a) by reaction with propargyl alcohol.

The present invention relates to a highly convergent method for the synthesis and purification of ceftolozane and intermediates starting from 7-aminocephaiosporanic acid (7-ACA).

Provided herein is a method for the synthesis of cephalosporin antibiotic compounds comprising a palladium-catalyzed coupling reaction. Provided herein are methods for the synthesis of cephalosporin compounds of formula (I) employing a palladium-catalyzed alkylation reaction, as well as compositions related to the same. In an aspect, provided herein is a method for preparing a compound of formula (II), or a salt thereof, comprising the step of admixing, e.g., reacting, a compound of formula (III), or a salt thereof, with a nucleophile (Nuc) in the presence of reagents comprising: (a) a palladium source; and (b) a palladium-binding ligand, to form a compound of formula (II), or a salt thereof.