Process for the preparation of carbapenem using cabapenem intermediates and recovery of cabapenem

A process for the preparation of a compound of formula II:

• or a pharmaceutically acceptable salt thereof, wherein R is hydrogen or a protecting group removed by hydrogenolysis and M and M′ are hydrogen, sodium ion, or potassium ion respectively;
• comprising:
• i) providing a compound of formula Ia:
• ii) converting the compound of formula Ia into the compound of formula II, wherein Ar is 2,4-dichlorophenyl, P is phosphor, and P′ is selected from the group consisting of alkyl, 2,2,2,-trichloroethyl, 2-bromoethyl, benzhydryl, trityl, aryl, trimethylsilyl, triethylsilyl, 4-methoxybenzyl, t-butyl, p-nitrobenzyl, hydrogen, and the like;
• and wherein the converting comprises the step of condensing the compound of formula Ia with a compound of formula V:
• to form a compound of formula VI:
• wherein P″ is selected from the group consisting of alkyl, 2,2,2,-trichloroethyl, dibromoethyl, benzhydryl, trityl, aryl, trimethylsilyl, triethylsilyl, 4-methoxybenzyl, t-butyl, p-nitrobenzyl, hydrogen, and the like and,
• wherein the compound of formula VI is converted into the compound of formula II by hydrogenolysis in presence of a metal catalyst, a base, water and a first organic solvent to produce a first solution of the compound of formula II, and the compound of formula II is obtained from the first solution of the compound of formula II by (a) filtering out the metal catalyst after adjusting a pH value of the first solution of the compound of formula II;
• (b) removing the first organic solvent from the first solution of the compound of formula II by distillation or extraction;
• (c) extracting with an alcohol after adding a second organic solvent in the first solution of the compound of formula II to produce a concentrated extract, and purifying and isolating with to a crystallization solvent to obtain the compound of formula II, and
• wherein the first organic solvent is selected from the group consisting of tetrahydrofuran, acetonitrile, ethylacetate, propionitrile, n-butanol, methanol, ethanol, dichloromethane, NN-dimethylformamide, N-ethylpyrrolidinone, and mixtures thereof;
• and
• the second organic solvent is selected from the group consisting of tetrahydrofuran, acetonitrile, ethylacetate, propionitrile, dichloromethane, NN-dimethylformamide, n-butanol, isoamyl alcohol, and mixtures thereof.

A process for the preparation of a compound of Meropenem:

• , comprising:
• i) providing a compound of formula Ia:
• ii) converting the compound of formula Ia into Meropenem, wherein Ar is 2,4-dichlorophenyl, P is phosphor, and P′ is selected from the group consisting of alkyl, 2,2,2,-trichloroethyl, 2-bromoethyl, benzhydryl, trityl, aryl, trimethylsilyl, triethylsilyl, 4-methoxybenzyl, t-butyl, p-nitrobenzyl, hydrogen, and the like;
• and wherein the converting comprises the step of condensing the compound of formula Ia with a compound of formula VII:
• to form a compound of formula VIII:
• wherein P″ is selected from the group consisting of alkyl, 2,2,2,-trichloroethyl, 2-bromoethyl, benzhydryl, trityl, aryl, trimethylsilyl, triethylsilyl, 4-methoxybenzyl, t-butyl, p-nitrobenzyl, hydrogen and the like.

A process for the preparation of a compound of Doripenem:

• , comprising:
• i) providing a compound of formula Ia:
• ii) converting the compound of formula Ia into Doripenem, wherein Ar is 2,4-dichlorophenyl, P is phosphor, and P′ is selected from the group consisting of alkyl, 2,2,2,-trichloroethyl, 2-bromoethyl, benzhydryl, trityl, aryl, trimethylsilyl, triethylsilyl, 4-methoxybenzyl, t-butyl, p-nitrobenzyl, hydrogen, and the like;
• and wherein the converting comprises the step of condensing the compound of formula Ia with a compound of formula IX:
• to form a compound of formula X:
• wherein P″ is selected from the group consisting of alkyl, 2,2,2,-trichloroethyl, 2-bromoethyl, benzhydryl, trityl, aryl, trimethylsilyl, triethylsilyl, 4-methoxybenzyl, t-butyl, p-nitrobenzyl, hydrogen and the like.