Single isomer methylphenidate and resolution process

Abstract

Single isomer methylphenidate, selected from the d-threo and l-threo-enantiomers, has been obtained in purified form, to the extent of less than 2% by weight of a contaminant selected from resolving agent and ritalinic acid. This is achieved by resolution of a mixture of enantiomers using an O,O′-diaroyltartaric acid as resolving agent.

We claim:  
     
         1 . A single isomer methylphenidate compound, selected from the group consisting of the d-threo- and l-threo-enantiomers, and pharmaceutically-acceptable salts thereof, wherein said compound is at least about 98% pure.  
     
     
         2 . The methylphenidate compound according to  claim 1 , wherein said compound is at least about 99% pure.  
     
     
         3 . The methylphenidate compound according to  claim 1 , wherein said compound is at least about 99.5% pure.  
     
     
         4 . The methylphenidate compound according to  claim 1 , wherein said compound is at least about 99.9% pure.  
     
     
         5 . The methylphenidate compound according to  claim 1 , wherein said compound is in the free base form.  
     
     
         6 . The methylphenidate compound according to  claim 1 , wherein said compound is in the hydrochloride form.  
     
     
         7 . A process for preparing substantially single enantiomer d-threo-methylphenidate or l-threo-methylphenidate, which comprises resolution of a mixture of enantiomers using an O,O′-diaroyltartaric acid as a resolving agent.  
     
     
         8 . The process according to  claim 7 , which additionally comprises salt cracking using aqueous alkali metal hydroxide.  
     
     
         9 . A pharmaceutical composition comprising d-threo-methylphenidate, or a pharmaceutically-acceptable salt thereof, and a pharmaceutically-acceptable diluent or carrier.  
     
     
         10 . The pharmaceutical composition according to  claim 9 , wherein said d-threo-methylphenidate is at least about 98% pure.  
     
     
         11 . The pharmaceutical composition according to  claim 9 , wherein said d-threo-methylphenidate is at least about 99% pure.  
     
     
         12 . The pharmaceutical composition according to  claim 9 , wherein said d-threo-methylphenidate is at least about 99.5% pure.  
     
     
         13 . The pharmaceutical composition according to  claim 9 , wherein said d-threo-methylphenidate is at least about 99.9% pure.  
     
     
         14 . The pharmaceutical composition according to  claim 9 , wherein said d-threo-methylphenidate is in the free base form.  
     
     
         15 . The pharmaceutical composition according to  claim 9 , wherein said d-threo-methylphenidate is in the hydrochloride form.  
     
     
         16 . A method for treating a person having a condition susceptible to treatment with methylphenidate comprising administering to the person an effective amount of d-threo-methylphenidate, or a pharmaceutically-acceptable salt thereof.  
     
     
         17 . The method according to  claim 16 , wherein said d-threo-methylphenidate compound is at least about 98% pure.  
     
     
         18 . The method according to  claim 16 , wherein said d-threo-methylphenidate compound is at least about 99% pure.  
     
     
         19 . The method according to  claim 16 , wherein said d-threo-methylphenidate compound is at least about 99.5% pure.  
     
     
         20 . The method according to  claim 16 , wherein said d-threo-methylphenidate compound is at least about 99.9% pure.  
     
     
         21 . The method according to  claim 16 , wherein said d-threo-methylphenidate is in the free base form.  
     
     
         22 . The method according to  claim 16 , wherein said d-threo-methylphenidate is in the hydrochloride form.  
     
     
         23 . The method according to  claim 16 , wherein the condition is selected from the group consisting of attention-deficient hyperactivity disorder and narcolepsy.