Abstract: The invention describes an improved process for the manufacture of a Flecainide intermediate viz N-(pyridin-2-ylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzamide (II). It consists of reacting 2,5-bis(2,2,2-trifluoroethoxy)benzoic acid with an acid chloride in a solvent mixture in presence of a base at ?10 to ?50° C. The resulting mixed anhydride is then condensed with 2-aminomethylpyridine at ?10 to ?40° C. and the resulting product after aqueous workup is purified by crystallization. This affords the intermediate II in vastly improved yields and quality. The intermediate II on catalytic hydrogenation affords N-(2-piperidinylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzamide (Flecainide), isolated as its acetate.

Abstract: Process for the manufacture of 1-[[[(1R)-1-[3-[(1E)-2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-3-[2-(1-hydroxy-1-methylethyl)phenyl]propyl]thio]methyl]cyclopropane acetic acid, sodium salt [montelukast sodium (I)] consisting of: i. Converting methyl 1-(mercaptomethyl)-cyclopropaneacetate to a metal salt (X) using a metal hydroxide, ii. Subjecting the metal salt (X) to monometallation to provide a dimetallide (XI). iii. Converting a diol of formula (II) to a mesylate of formula (III) and reacting (III) in situ with (XI) affordin the metal salt of 1-[[[(1R)-1-[3-[(1E)-2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-3-[2-(1-hydroxy-1-methylethyl)phenyl]propyl]thio]methyl]cyclopropane acetic acid. iv. Reacting the metal salt in-situ with a base and purifying to afford an amine salt (XII). v. Treating (XII) with a sodium base and precipitating out montelukast sodium (I).

Abstract: An improved process for the manufacture of 1-[[[(1R)-1-[3-[(1E)-2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-3-[2-(1-hydroxy-1-methylethyl)phenyl]propyl]thio]methyl]cyclopropane acetic acid, sodium salt [montelukast sodium(I)]. It consists of converting a vital intermediate 1-(mercaptomethyl)-cyclopropane acetic acid of formula IX, to a quaternary ammonium salt of formula X, using a suitable base in a suitable solvent at 0° C. to 50° C. followed by monometalation to provide an intermediate of formula XI and subsequent condensation of XI with 2-[2-[3-(S)-[3-[2-(7-chloro-2-quinolinyl)-ethenyl]phenyl]-3-methanesulphonyloxypropyl]phenyl]-2-propanol at 0 to ?50° C.

Abstract: A process for the manufacture of the antibiotic 7-(D-.alpha.-amino-.alpha.-phenylacetamido)-3-methyl-3-cephem-4-carboxylic acid (cephalexin) and pharmaceutically acceptable salts thereof. It consists of reacting an enamine protected potassium salt of D-(-)-.alpha.-phenyl glycine (Dane salt) with an acid chloride in a twin solvent mixture in the presence of a pyridine derived twin catalytic mixture at -20 to -65.degree. C. The resulting mixed anhydride is condensed with an alkyl guanidinium salt solution of 7-amino desacetoxy cephalosporanic acid (7-ADCA) at -10.degree. C. to -65.degree. C. followed by hydrolytic cleavage of the enamine derivative of the resulting compound with an aqueous mineral acid and precipitation of the antibiotic in the presence of an alcohol as co-solvent. If desired the cephalexin is converted into its pharmaceutically acceptable salts in a known manner.