Coupling process and intermediates useful for preparing cephalosporins

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

or a pharmaceutically acceptable salt thereof, wherein the group CO 2 R 1 is a carboxylic acid or a carboxylate salt; and R 2 has the formula

comprising reacting a compound of formula II

 with a compound of the formula III

R 2 L  III

 wherein R 2 is as defined above; and

L is di-(C 1-6 alkyl)phosphorothioate; in the presence of a solvent and a base.

2. The process according to claim 1 further comprising the step of preparing said compound of formula II by reacting a compound of formula IV:

wherein R 3 is para-nitrobenzyl or allyl; and X is halo;

with a suitable deprotecting agent; in the presence of a solvent.

3. A process according to claim 1 , wherein L of said compound of the formula III is diethylphosphorothioate.

4. A process according to claim 1 , wherein said solvent is acetone.

5. A process according to claim 1 wherein said base is sodium hydroxide.

6. A process according to claim 2 , wherein X is chloro.

7. A process according to claim 2 , wherein said R 3 is para-nitrobenzyl and said suitable deprotecting agent is sodium dithionite or a catalytic hydrogenating agent.

8. A process according to claim 2 , wherein said R 3 is allyl and said suitable deprotecting agent is tetrakis triphenylphosphine palladium (0).

9. A process according to claim 7 , wherein said solvent is acetone, water, tetrahydrofuran or mixtures thereof.

10. A compound of formula II:

11. The compound according to claim 10 wherein said compound of the formula II has an enantiomeric or diasteriomeric purity of 96% to 100%.

12. A process according to claim 2 wherein R 3 is para-nitrobenzyl.