EP1554287A1 — Process for preparation of penam derivatives from cepham derivatives

USPTO Abstract

The present invention provides a novel process for preparing a 2b-heterocyclyl methyl penam derivatives of the formula (I): (I)where R1 represents hydrogen, carboxylic acid protecting group such as an ester or a pharmaceutically acceptable salt; R2 and R3 may be same or different and independently represent hydrogen, halogen, NH2, acylamino, phthalimido with a proviso that both R2 and R3 are not NH2, acylamino, phthalimido; Het represents a 5 or 6-membered NH containing heterocycle ring system containing one or more heteroatoms selected from O, S, or N, which comprises :(i) reacting a compound of formula (VII) where L represents a leaving group with a compound of formula (VIII) where Het is as defined earlier in the presence of a solvent and base at a temperature in the range of -10 to 110 °C to produce a compound of formula (IX); (ii) oxidizing the compound of formula (IX) using conventional oxidizing agents in the presence of water miscible solvent and an organic acid to produce a compound a formula (I) and if necessary; and (iii) de-esterifying the compound of formula (I) where R1 represents a carboxy protecting group to a compound of formula (I) where R1 represents hydrogen using metal catalyst, in the presence of a base and water immiscible solvent.