Process for halogenation of .beta.-lactam compounds

A process for preparing a compound of the formula ##STR34## which comprises reacting a compound of the formula ##STR35## with about 1.0 to about 1.3 equivalents of a chlorinating compound of the formula ##STR36## which (a) has a .sup.31 P nuclear magnetic resonance signal in methylene chloride at -3.7 ppm relative to that of phosphoric acid;

• (b) has in methylene chloride an infrared spectrum which has the following characteristic absorptions:
• 1120-1190 (very strong), 1070 (very strong), 1035 (strong), 1010 (very strong), 990 (very strong), 640 (medium) 625 (medium), 580 (weak), 510 (strong) and 465 (weak);
• (c) reacts with water to give HCl and triphenyl phosphate;
• and
• (d) reacts with n-butanol to give HCl, n-butyl chloride, and triphenyl phosphate;
• in a substantially anhydrous inert organic solvent at a temperature below about 30.degree. C. wherein in the above formulas
• R is a carboxylic acid protecting group;
• R.sub.1 is hydrogen or methoxy;
• and ##STR37## amino protecting group;
• or R.sub.2 is hydrogen or an acyl group derived from a carboxylic acid;
• and
• R.sub.3 is an acyl group derived from a carboxylic acid;
• or
• R.sub.2 and R.sub.3 taken together with the nitrogen atom to which they are attached form a group of the formula ##STR38## wherein R.sub.4 is the residue of an acyl group derived from a dicarboxylic acid;
• provided that when R.sub.2 and R.sub.3 are substituted by amino, hydroxy or carboxy groups, those groups are first protected by one of the conventional amino, hydroxy or carboxy protecting groups.

A process for preparing an imino halide compound of the formula ##STR39## which comprises reacting a compound of the formula ##STR40## with about 2.0 to about 3.0 equivalents of a halogenating compound of the formula ##STR41## which is the kinetically controlled product of the reaction, in a substantially anhydrous inert organic solvent, of equivalent amounts of a triaryl phosphite of the formula ##STR42## and chlorine or bromine, in the presence of about 1.0 to about 1.2 equivalent of a tertiary amine base per equivalent of halogenating compound employed, in a substantially anhydrous inert organic solvent at a temperature below about 30.degree. C. wherein the above formulas

• X is Cl or Br;
• Z is hydrogen, halo, C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkoxy;
• R is a carboxylic acid protecting group;
• R.sub.1 is hydrogen or methoxy;
• and R.sub.7 is the residue of an acyl group derived from a carboxylic acid;
• provided that when R.sub.7 is substituted by amino, hydroxy or carboxy groups, those groups are first protected by one of the conventional amino, hydroxy, or carboxy protecting groups.

A process for preparing an imino halide compound of the formula ##STR43## which comprises reacting a compound of the formula ##STR44## with about 2.0 to about 3.0 equivalents of chlorinating compound of the formula ##STR45## which (a) has a .sup.31 P nuclear magnetic resonance signal in methylene chloride at -3.7 ppm relative to that of phosphoric acid;

• (b) has in methylene chloride an infrared spectrum which has the following characteristic absorptions:
• 1120-1190 (very strong), 1070 (very strong), 1035 (strong), 1010 (very strong), 990 (very strong), 640 (medium) 625 (medium), 580 (weak), 510 (strong) and 465 (weak);
• (c) reacts with water to give HCl and triphenyl phosphate;
• and
• (d) reacts with n-butanol to give HCl, n-butyl chloride, and triphenyl phosphate;
• in the presence of about 1.0 to about 1.2 equivalent of a tertiary amine base per equivalent of chlorinating compound employed, in a substantially anhydrous inert organic solvent at a temperature below about 30.degree. C. wherein in the above formulas
• R is a carboxylic acid protecting group;
• R.sub.1 is hydrogen or methoxy;
• and R.sub.7 is the residue of an acyl group derived from a carboxylic acid;
• provided that when R.sub.7 is substituted by amino, hydroxy or carboxy groups, those groups are first protected by one of the conventional amino, hydroxy, or carboxy protecting groups.