Process for producing 3-chloromethyl-3-cephem derivatives

A process for preparing a 3-chloromethyl-3-cephem derivative comprising the following first to third steps:

• First step:
• reacting a thiazoline azetidinone derivative with a sulfonyl halide in a solvent and in the presence of an acid to produce an azetidinone derivative, the thiazoline azetidinone derivative being expressed by Chemical Formula (1):
• wherein R1 and R2 each represent an aromatic hydrocarbon group, sulfonyl halide being expressed by Chemical Formula (2):
• R3—SO2X (2)
• wherein R3 represents one selected form the group consisting of substituted or unsubstituted aryl groups and substituted or unsubstituted heterocyclic residues, and X represents a halogen atom, and the azetidinone derivative being expressed by Chemical Formula (3):
• wherein R1, R2 and R3 are the same as described above;
• Second Step:
• reacting the azetidinone derivative obtained by the first step with a chlorination agent in an organic solvent to produce a chlorinated azetidinone derivative, the chlorinated azetidinone derivative being expressed by Chemical Formula (4):
• wherein R1, R2 and R3 are the same as described above;
• and
• Third Step:
• reacting the chlorinated azetidinone derivative obtained by the second step with an alcoholate in a solvent containing an alcohol and an ether at a pH of 8 or less to produce a 3-chloromethyl-3-cephem derivative in a crystal form, the alcoholate being expressed by Chemical Formula (5):
• R4—OM (5)
• wherein R4 is an organic group and M is an alkali metal atom, and the 3-chloromethyl-3-cephem derivative being expressed by Chemical Formula (6):
• wherein R1, R2 and R3 are the same as described above.