Process for The Preparation of Beta-Lactam Antibiotic
AssigneeOrchid Chemicals & Pharmaceuticals Limited
InventorsSenthilkumar Surulichamy, Selvakumar Sekar, Pramod Narayan Deshpande, Panchapakesan Ganpathy, Rajendra Janardan Sarangdhar, Syril Sudhan Henry, Sanjay Nivruti Karale, Arvind Atmaram Jangale, Ram Dattatray Kaldate
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Abstract
The present invention relates to a process for the preparation of Meropenem of formula (I) in sterile form and also provides an improved process for the preparation of compound of formula (V), which is an important intermediate in the synthesis of Meropenem.
Claims15
A process for the preparation of highly pure sterile Meropenem trihydrate of the formula (I), which comprises the steps of:
- (a) dissolving the Meropenem or its hydrate salt in water in the presence of base and in the presence or absence of water-miscible organic solvents,
- (b) optionally filtering through micron filter,
- (c) adjusting the pH to 4.0 to 7.0, and
- (d) optionally adding solvent to yield the Meropenem trihydrate of formula (I).
An improved process for preparing Meropenem of the formula (I), the said process comprising the steps of:
- i) activating the compound of formula (II)
- using diphenyl chlorophosphate in the presence or absence of base and solvent to produce compound of formula (III),
- ii) reacting the activated compound of formula (III) with mercaptan of formula (IV)
- in the presence or absence of base and solvent to yield compound of formula (V);
- and
- iii) isolating the compound of formula (V) by quenching with water, and
- iv) deprotecting the compound of formula (V) by catalytic hydrogenation in the presence of solvent to yield compound of formula (I).
An improved process for preparation of compound of formula (V), which comprises the steps of:
- 1. reacting the activated compound of formula (III) with mercaptan of formula (IV) in the presence or absence of base in a water-miscible organic solvent to yield compound of formula (V),
- 2. quenching the reaction mass from step (1) in water in the presence or absence of buffer,
- 3. optionally adjusting the pH of step (2) mass to 3.0 to 5.0, and
- 4. filtering the compound of formula (V).
A novel amorphous form of (4R,5S,6S,8R,2′S,4′S)-p-nitrobenzyl-3-[4-(1-p-nitrobenzyloxycarbonyl-2-dimethylaminocarbonyl)pyrrolidinylthio]-4-methyl-6-(1-hydroxyethyl)-1-azabicyclo[3.2.0]hept-2-en-7-one-2-carboxylate of formula (V).
(canceled)
Dependencies are inferred from the claim text.