PURPOSE: To obtain the subject compound useful as a synthetic intermediate for antimicrobial agents by reacting a hydroxymethylcarbapenem compound with a phosphorylating agent and then reacting the resultant product with a halogenating agent.
CONSTITUTION: A 2-hydroxymethylcarbapenem compound expressed by formula I [R1 and R2 are H or (substituted) alkyl; R5 is H or carboxy-protecting group] is reacted with a phosphorylating agent in the presence of an acid capturing agent (e.g. dimethylaminopyridine), preferably at -60 to -20°C for 30min to 3hr to provide a 2-phosphoryloxymethylcarbapenem compound expressed by formula II [R3 and R4 are halogen, (substituted) alkoxy or aryloxy], which is subsequently reacted with a halogenating agent (e.g. an alkali metallic halide), preferably at -40°C to ambient temperature for 30min to 3hr to afford the objective 2-halomethylcarbapenem compound expressed by formula III (Hal is halogen).
IMUDA MITSURU
ONA TOSHIO
ITANI HIKARI
