Browse Prior Art Database

A PROCESS FOR THE ENANTIOMERIC RESOLUTION OF A TETRAHYDROBENZAZEPINE COMPOUND

IP.com Disclosure Number: IPCOM000236134D
Publication Date: 2014-Apr-08
Document File: 4 page(s) / 81K

Publishing Venue

The IP.com Prior Art Database

This text was extracted from a Microsoft Word document.
At least one non-text object (such as an image or picture) has been suppressed.
This is the abbreviated version, containing approximately 49% of the total text.

A PROCESS FOR THE ENANTIOMERIC RESOLUTION OF A TETRAHYDROBENZAZEPINE COMPOUND

[0001]          Lorcaserin is an active pharmaceutical substance with an empirical formula of C11H14NCl and a molecular weight of 195.69. Lorcaserin is the international commonly accepted non-proprietary name for (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine, which is represented by Formula (I):

(I)

[0002]          The present document discloses a process for the enantiomeric resolution of Lorcaserin, said process comprising:

a)       contacting a mixture of (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine and (S)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine with L-(+)-tartaric acid, in a suitable solvent;

b)       precipitating the L-(+)-tartaric acid salt of (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine; and

c)       optionally, repeating steps (a) and (b) as hereinbefore described;

wherein the solvent is selected from the group comprising alcohols, water and/or mixtures thereof.

[0003]          Preferred alcohol solvents for the process as hereinbefore described are selected from the group comprising methanol, ethanol, isopropanol, 1-propanol, 1-butanol, tert-butanol, 2-methyl-2-butanol and/or mixtures thereof.

[0004]          A particularly preferred solvent for the process as hereinbefore described comprises a mixture of ethanol and water, a mixture of isopropanol and water, or a mixture of 2-methyl-2-butanol and water.

[0005]          The initial mixture of (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine and (S)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine preferably comprises an equimolar mixture (i.e. racemic Lorcaserin) of both enantiomers. Alternatively, the initial mixture of (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine and (S)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine can also comprise an enantiomerically enriched mixture where one of the two enantiomers is in a greater amount that the second one and consequently is characterized by having an enantiomeric excess value greater than 0%. The enantiomeric excess value is calculated as the absolute value of the result of formula ((RS) / (R + S)) x 100, where R and S are the mole fractions of (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine and (S)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine in the mixture, respectively. Preferably, the enantiomeric excess value of the enantiomerically enriched mixture of (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine and (S)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine is greater than about 50%, more preferably greater than about 90%, even more preferably greater than about 95%, and still more preferably greater than about 99%. Preferably, the enantiomerically enriched mixture contains a higher amount of (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine than (S)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine.

[0006]          Precipitation of the L-(+)-tartaric acid salt of (R)-8-chloro-1-methyl-2,3,4,5-t...