Patent ID: 7470786

Claim:
A process for the preparation of ceftriaxone sodium of formula (II), comprising the steps of i) reacting a silylated compound of formula (III), with a 4-halo-2-methoxyimino-3-oxo-butyric acid derivative of formula (IV), wherein X and Y represent a halogen atom to give a compound of formula (V), ii) desilylating the compound of formula (V), wherein X is as defined hereinabove to give the desilylated compound of formula (VI), iii) reacting the desilylated compound of formula (VI) with thiourea in a solvent system containing organic solvent and water, to obtain ceftriaxone of formula (I), iv) converting the compound of formula (I) to the sodium salt (II); wherefore the improvement comprises i 1 ) reacting a silylated compound of formula (III), with a 4-halo-2-methoxyimino-3-oxo butyric acid derivative of formula (IV) having a purity of at least 95%, said 4-halo-methyloxyimino-3-oxo-butyric acid derivative containing 0.50% or less total di-brominated and poly-brominated impurity compounds, wherein X represents Br and Y represents Cl, in the presence of an inert water-immiscible organic solvent or mixtures thereof and in the presence of an acid scavenging agent at a temperature of between −10° C. to −0° C. to give a compound of formula (V), ii 1 ) adding the solution of compound of formula (V) in the inert water-immiscible organic solvent or mixtures thereof to a 1:1 mixture of water and a water-immiscible organic solvent and separation of the organic phase to provide a solution of compound of formula (VI) in the inert water-immiscible organic solvent or mixtures thereof, iii 1 )reacting the solution of compound of formula (VI) in the inert water-immiscible organic solvent admixed with a solution of thiourea in water, adding an alkali metal containing inorganic base at a temperature of between 0° C. to +10° C., maintaining the reaction mixture at a pH ranging between 5.0 to 5.5, and removing the organic layer to provide a solution of the alkali metal salt of ceftriaxone of formula (II 1 ) in water, wherein M is an alkali metal, iv 1 )mixing the solution of the alkali metal salt of ceftriaxone (II 1 ) in water with a water-immiscible organic solvent and a water-miscible solvent and treating the solution thus obtained with an acid to a pH of 3.6 to 4.0 and isolating the precipitated ceftriaxone of formula (I) by filtration, v 1 ) reacting solution of ceftriaxone of formula (I) in water with an organic amine maintaining a pH of 5.4±0.2 to produce a solution of the amine salt of ceftriaxone in water of formula (VII), wherein Q + represents the protonated organic amine, and (vi 1 ) reaction of the amine salt of ceftriaxone of formula (VII) in a mixture of water and a water-miscible organic solvent with a sodium ion carrier to give after crystallization ceftriaxone sodium of formula (II)