Coupling process and intermediates useful for preparing cephalosporins

A process for preparing a 3-cyclic-ether-substituted cephalosporin of the formula I:

• 30
• or a pharmaceutically acceptable salt thereof,
• wherein
• the group CO2R1 is a carboxylic acid or a carboxylate salt;
• and
• R2 has the formula:
• 31
• wherein
• A1 is selected from the group consisting of C6-10aryl, C1-10heteroaryl and C1-10heterocyclyl;
• A2 is selected from the group consisting of hydrogen, C1-6alkyl, C3-10cycloalkyl, C6-10aryl, C1-6alkyl(CO)(C1-6)alkyl-O—, HO(CO)(C1-6)alkyl, mono-(C6-10aryl)(C1-6alkyl), di-(C6-10aryl)(C1-6alkyl), and tri-(C6-10aryl)(C1-6alkyl);
• comprising reacting a compound of formula II:
• 32
• with a compound of the formula III:
• R2L III
• wherein
• R2 is as defined above;
• and
• L is selected from the group consisting of hydroxy, halo, azido, mono(C1-6alkyl)carbonate, (C1-6alkyl)carboxylate, (C6-10aryl)carboxylate, mono-(C6-10aryl)(C1-6alkyl)carboxylate, di-(C6-10aryl)(C1-6alkyl)carboxylate, di(C1-6alkyl)phosphorothioate, (C1-6alkyl)sulfonyl, mono-(C1-6alkyl)(C6-10aryl)sulfonyl, di-(C1-6alkyl)(C6-10aryl)sulfonyl, (C1-6-alkyl)-(CO)—S—, cyano-C1-6alkoxy, C6-10aryloxy, 3-benzthiazolytoxy, 8-quinolinyloxy and N-oxy-succinimidyl;
• in the presence of a solvent, a base, an optional coupling agent and an optional catalyst.