Cephalosporin derivs. prepn. - by acylating a cephalosporin with the 7-amino and carboxyl gps. protected with boron-contg. gps.

摘要

Prepn. of cephalosporins comprises mixing (a) at room temp. a cephalosporin deriv. of formula (I):- (where R is H, OCOMe, (II) or (III)) with a polar, anhyd. organic solvent which is MeCNM, THF, CH2Cl2 and/or CHCl3 and a tert. or sec. organic base which is a di- and/or trialkylamine; (b) cooling the mixt. to -45 to -25 degrees C; (c) adding >=2 mol/mol (I) of ethylene chloroborate, propylenechloroborate or phenylene chloroborate; and (d) raising the temp. to 0 degrees C to give a new intermediate. Process further comprises (e) acylating the intermediate at -10 to 0 degrees C, e.g. with the hydrochloride of D-(-)-alpha-amino-p-hydroxy-alpha-phenylacetic acid chloride, the hydrochloride of D(-)-alpha-amino-alpha-phenylacetic acid chloride or the hydrochloride of D(-)-alpha-amino-(1,4-cyclohexadienyl) acetic acid chloride and (f) adding a mixt. of water and water soluble alcohol to form an aq. soln. The cephalosporin cpd. is isolated from this aq. soln. Process is simple and neither the use of organic bases or the chemical reactions lead to removal of the carboxyl gp. protecting gps.