Preparation of desclarithromycin from erythromycin, for use as antibiotic intermediate, comprises five stage process via new silylated and/or N-oxide intermediates

摘要

Preparation of desclarithromycin (I) involves: (1) reacting erythromycin A with silylating agent to give silylated derivative (IX); (2) oxidizing to give silylated N-oxide (X); (3) ethylating under basic conditions to give 6-O-methylated derivative (XI); (4) subjecting to acid hydrolysis to give desclarithromycin N-oxide (XII); and (5) reducing. The intermediates (X), (XI) and (XII) are new. Preparation of desclarithromycin of formula (I) involves: (1) reacting erythromycin A with R3SiCl and/or R3Si-imidazole or (R3Si)2NH or R3SiOSO2CF3 under basic conditions to give a silylated derivative of formula (IX); (2) oxidizing to give the N-oxide of formula (X); (3) reacting with a methylating agent under basic conditions to give the O-methylated derivative of formula (XI); (4) subjecting (XI) to acid hydrolysis to give desclarithromycin N-oxide of formula (XII); and (5) reducing. R = Me or Et; R' = H or SiR3. The order of stages (a) and (b) and/or stages (d) and (e) may be reversed. Independent claims are included for: (1) the intermediates (X), (XI) and (XII) as new compounds; and (2) the preparation of (X) as in step (b) or by carrying out step (a) in presence of an oxidizing agent.