Pharmaceutically active morpholinol
AssigneeSmithKline Beecham Corporation
InventorsToby Broom, Monica Delpogetto, Richard Atkins, Alan Negus, Paul William Oxley
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Abstract
Disclosed is the compound (+)-(2S,3S)-2-(3-chlorophenyl)-3,5,5-trimethyl-2-morpholinol and pharmaceutically acceptable salts and solvates thereof, methods for preparing them, pharmaceutical compositions comprising them, and processes for their preparation; also disclosed is a method of treating depression, attention deficit hyperactivity disorder (ADHD), obesity, migraine, sexual dysfunction, Parkinson's disease, Alzheimer's disease, or addiction to cocaine or nicotine-containing (especially tobacco) products using such compound, salts, solvates or compositions.
Claims18
A process for preparing optically pure (+)-(2S, 3S)-2-(3-chlorophenyl)-3,5,5-trimethyl-2-morpholinol or a pharmaceutically acceptable salt or solvate thereof which comprises
- treating racemic 2-(3-chlorophenyl)-3,5,5-trimethyl-2-morpholinol with di-p-toluyl-L-tartaric acid under suitable reaction conditions and in a solvent to form a mixture of diastereomeric salts, wherein the solvent comprises at least one solvent selected from the group consisting of ethanol, ethanol and water, industrial methylated spirit (IMS), and acetonitrile;
- isolating from the mixture of the diastereomeric salts a chiral salt of (+)-(2S, 3S)-2-(3-chlorophenyl)-3,5,5-trimethyl-2 -morpholinol;
- and
- contacting the chiral salt of (+)-(2S, 3S)-2-(3-chlorophenyl)-3,5,5-trimethyl-2-morpholinol with a base.
A process for preparing optically pure (S,S)-2-(3-chlorophenyl)-2-hydroxy-3,5,5-trimethyl-morpholinol or a pharmaceutically acceptable salt or solvate thereof which comprises:
- brominating 3-chloropropiophenone to form an intermediate;
- contacting the intermediate with 2-amino-2-methyl-1-propanol under suitable reaction conditions and in a suitable solvent for the formation of racemic 2-(3-chlorophenyl)-2-hydroxy-3,5,5-trimethyl-morpholinol, wherein said solvent comprises at least one solvent selected from the group consisting of ethanol, ethanol and water, industrial methylated spirit (IMS), and acetonitrile;
- contacting the racemic 2-(3-chlorophenyl)-2-hydroxy-3,5,5-trimethyl-morpholinol with di-p-toluyl-L-tartaric acid under suitable reaction conditions to form a mixture of diastereomeric salts;
- isolating from the mixture of the diastereomeric salts a chiral salt of (S,S)-2-(3-chlorophenyl)-2-hydroxy-3,5,5-trimethyl -morpholinol;
- and
- contacting the chiral salt of (S,S)-2-(3-chlorophenyl)-2-hydroxy-3,5,5-trimethyl-morpholinol with a base.
Dependencies are inferred from the claim text.