Grignard Reaction
Specific technology has been developed to synthesize Grignard reagent by in situ activation of magnesium. With the activated magnesium, Grignard reagent can be formed at low temperatures. Facilities are there to generate Grignard reagent in refluxing too. Non-aqueous cooling medium is used in the condenser for safety reasons.

Friedel-Craft Reaction
Facilities are adequate for in situ generation of the acid chloride required for Friedel-Craft Reaction. HPLC method is developed to monitor in situ formation of acid chloride through derivatisation since acid chloride is not stable under reverse phase HPLC conditions.

Catalytic Hydrogenation
Hydrogenator of 2000 ltrs capacity is available for hydrogenation. Pyrophoric palladium carbon is handled in a safe manner. Reductive amination coupled with debenzylation is carried out in one-pot reaction. Differences in situ generated intermediates are monitored by GC. and Cyanogroup of a highly substituted ester derivative is reduced to a primary amino group in the presence of Raney nickel at a pressure of 6-8 Kg/cm2

Cyanation
Cyanations are carried out in homogeneous and biphasic media. A proper method of effluent treatment has been developed for destruction of residual cyanides.

Bromination
Bromination of the active methylene group is a tricky reaction as there is a possibility of formation of dibromo derivatives.Suitable reaction condition at commercial scale have been developed for the optimum formation of the desired product.

Wolff-Kishner Reduction
Ketone of one of the intermediates is reduced using hydrazine hydrate and sodium hydroxide.Appropriate temperature condition have been established at commercial scale to get optimum yield of the product.

Michael Reaction
Dialkylation of primary amine is carried out with ethyl acrylate and the Resulting dialkylated product is used in subsequent step without purification. Excellent technology has been stabilized on commercial scale to obtain quality dialkylamine without purification under Michael reaction.Similarly technology for synthesizing highly substituted 1,4-diketones involving the Michael addition of aromatic aldehydes to activated olefins under the Steller catalytic condition have been successfully scaled up.

Carbon Homologation
Low temperature experimental conditions involving coupling of n-butyl lithium/diisopropylamine generated carbanion derived from esters with hydroxy substituted esters leading to ß-ketoester via a 2-carbon homologation have been scaled up.A similar transformation involving the reaction of a dianion generated from a ß-ketoester (in the presence of sodium hydride/n-butyllithium at low temperatures) with an aldehyde provides advanced pharmaceutical intermediate via a 4-carbon homologation methodology.

Intermolecular Cyclization
Acid assisted experimental conditions have been developed for the cyclization of tetrasubstituted 1,4-diketones with a highly functionalized primary amine in a ternary solvent system to provide an advance pyrrole derivative in a reasonably good yield.

Intramolecular Cyclization
A highly concentrated solution of an N-alkylated aromatic ketone derivative is forced to undergo intramolecular cyclisation in the presence of a transition metal salt to yield an indole derivative.

Ketalisation
Acid catalysed ketalisation of a highly sensitive 1,3-diol ester under very mild experimental conditions provides a very pure crystalline intermediate.

Deketalisation
Under extremely controlled and mild acidic conditions, protected ketal functionality of a highly sensitive substituted heterocyclic compound is selectively deprotected in the presence of tertiary butyl ester group to provide an advanced intermediate.

Condensation
A high yield synthesis of an activated trisubstituted olefin via condensation of a ß-ketoester derivative and aromatic aldehydes has been standardized under very mild conditions.

Amide Formation
Substituted ß-ketoester is reacted with aromatic amines under refluxing conditions to provide the amide derivative in high purity which is then straightway used in the next stage without further purification.

Methylation
Process for methylation using dimethylsulfate as a reagent has been commercialized incorporating all safety aspects.

Hydrolysis
Nitrile of one of the intermediate is hydrolysed to carboxylic acid giving almost quantitative yield at the commercial scale. In another intermediate ester is hydrolysed to give carboxylic acid.

Esterification
Conditions for esterification have been developed on commercial scale using different acids to give high purity product minimizing effluent and pollution load.

Reduction
Ester of one of the intermediate is reduced to alcohol using sodium borohydride activated with aluminium chloride. Process for ketone reduction to form a hydroxy group has been commercialized using sodium borohydride.

Stereoselective Reduction
Very low temperature experimental conditions (-90ºC to 100ºC) have been utilized to carry out stereoselective reduction of hydroxy substituted ß-ketoester in the presence of boranes and sodium borohydride to synthesize cis 1,3-diol derivatives. Higher temperatures lead to the formation of trans 1,3 diols in higher proportions which cannot be easily separated from the cis diol derivatives.

Morepen’s Strengths - Chemistry

Chiral Synthesis • Montelukast Sodium • Moxifloxacin Grignard reaction • Loratadine • Montelukast • Fexofenadine Hydrochloride Fridel Craft reaction • Loratadine • Fluvastatin Sodium • Fexofenadine Hydrochloride High pressure Hydrogenation • Atorvastatin Calcium • Pioglitazone Hydrochloride • Moxifloxacin Hydrochloride Low temperature stereo specific reduction • Atorvastatin Calcium • Fluvastatin Sodium 2 & 3 Carbon Homologation reactions • Atorvastatin Calcium • Fluvastatin Sodium Cyanation • Loratadine Merwein Arylation • Pioglitazone Hydrochloride Bromination • Sultamicillin Tosylate • Zafirlukast • Montelukast Sodium • Cisapride Alkylation • Montelukast Sodium • Fexofenadine Hydrochloride • Cisapride Hetero Cyclization • Atorvastatin Calcium • Pioglitazone Hydrochloride • Fluvastatin Sodium • Paroxetine Hydrochloride Vilsmair Haack reaction • Fluvastatin Sodium Nucleophilic substitution • Montelukast Sodium • Gatifloxacin Hydrochloride