Abstract:
The process exploits the high efficiency of the catalytic system consisting of copper(I) salt and an organic ligand in the presence of an inorganic base in the N-amidation reaction of chlorobenzene, a cheap reagent also usable as solvent in this case; reaction conditions at high temperatures, at atmosphere pressure or higher, produce a reaction with good yields.
Abstract:
Disclosed is a process for the industrial synthesis of Lurasidone from (1R,2R)-cyclohexane-1,2-diyldimethanol (1), 3-(piperazin-1- yl)benzo[d]isothiazole (3) and (3aR,4R,7R,7aS)-3a,4,7,7a-tetrahydro-4,7- methanoisobenzofuran-1,3-dione (6).). Said process is optimised to obtain Lurasidone with high yields and high purities by preparing highly pure synthesis intermediates, using critical raw materials and reagents in amounts close to the stoichiometric amounts, increasing productivity and reducing the costs and environmental impact of the process.
Abstract:
Disclosed is a process for the synthesis of lofexidine of formula (I) and the hydrochloride salt thereof (II), from ethyl 2-(2,6-dichlorophenoxy)propionate (III) and ethylenediamine in the presence of tetravalent titanium alkoxides, preferably titanium isopropoxide, in an apolar solvent such as toluene. A further object of the present invention is a process for the preparation of the intermediate ethyl 2-(2,6-dichlorophenoxy)propionate (III) from 2,6-dichlorophenol and ethyl 2-chloropropionate in the presence of a polar aprotic solvent and an alkali or alkaline earth carbonate salt, preferably potassium carbonate. Both processes are more cost-effective and more easily industrially scalable than the known procedures, thus enabling the active ingredient to be obtained with high yields at a limited cost.
Abstract:
Disclosed is a process for the synthesis of iloperidone starting from 4-hydroxy-3-methoxy acetophenone (acetovanillone), 1-chloro-3-bromo propane and 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole hydrochloride, using a one-pot method.
Said process is performed without any intermediate isolation, and is particularly advantageous from the environmental standpoint and in terms of yields, productivity and the purity of the product obtained, both in the reaction mixture and in the crystal isolated.
Abstract:
A process for the enantiomeric resolution of 1-substituted 2-(aminomethyl)pyrrolidines of formula (I)
in which R is C1-C6 alkyl, which process comprises the reaction of the racemic amine with benzyl acetate in acetonitrile in the presence of a lipase selected from Pseudomonas cepacia, Pseudomonas fluorescens or Candida rugosa lipases, to give the corresponding 1-substituted N-(pyrrolidin-2-yl-methyl)-acetamides of formula (II), with R configuration,
and the residual amine with S configuration, and, if desired, the subsequent hydrolysis of the amide to obtain the amine with R configuration.