Patent ID: 7064199

Claim:
A process for producing a vinylpyrrolidinone-cephalosporin derivative of formula A-1 wherein * denotes a center of chirality; comprising: (a) converting a compound of the formula II wherein X is a protected hydroxy group; Z 1 is an amino protecting group; and * is as above in the presence of hydroxylamine or an acid addition salt thereof into the N-hydroxy-pyrrolidine derivative of the formula III wherein Z 1 and * have the same meaning as above; (b) reducing said N-hydroxy derivative of formula III to the secondary amine derivative of formula IV wherein Z 1 and * have the same meaning as above by hydrogenation with Raney nickel; (c) converting said secondary amine of formula IV into a 3-amino pyrrolidine compound of formula I wherein R 1 is an amino protecting group and * is as above; by reaction of the 1-amino group of the compound of formula IV with a compound of formula R 1 X 1 , in which R 1 has the above indicated meaning, and X 1 is halogen or a leaving group, and deprotecting the resulting 3-amino group by catalytic hydrogenation; (d) reacting said 3-amino-pyrrolidine compound of formula I with 2-bromo-4-chlorobutanoylchloride to yield a compound of formula (1) wherein R 1 and * have the above indicated meaning (e) converting said compound of formula (1) into the corresponding triphenylphosphine Wittig salt of formula (2) wherein Ph is phenyl and R 1 and * are as above; (f) reacting said Wittig salt of formula (2) with a diprotected 3-ene cephalosporin derivative of formula (3) wherein BOC is tert.-butoxycarbonyl; and Ph is phenyl; to yield the condensation product (4) wherein *, BOC, R 1 and Ph are as above (g) oxidizing said condensation product of formula (4) to produce the 5-sulfoxide compound of formula (5) wherein *, R 1 , BOC and Ph are as above. (h) reducing the sulfoxide group on said 5-sulfoxide compound of formula (5) to form the 2-ene celphalosporin derivative of formula (6) wherein *, BOC and Ph are as above. (i) deprotecting the 7-amino group of said compound of formula (6) and acylating the deprotected compound of formula (6) with (Z)-(5-amino[1,2,4]thiadiazol-3-yl-trityloximino-thioacetic acid S-benzothiazol-2-yl ester to yield the compound of formula (1) wherein *, R 1 , Y and Ph are as above; and (j) removing the protecting amino protecting groups R 1 and CPh 3 from the compound of formula (9) to produce the compound of formula A-1.