Pharmaceutically useful (+)-1-(3-dimethylaminopropyl)-1-(4'-fluorophenyl)-1,3-dihydroiso benzofuran-5-carbonitrile and non-toxic acid addition salts thereof

Abstract

The two enantiomers of the anti-depressant drug of the formula I <IMAGE> are disclosed. Methods for resolving intermediates and their [steroselective] stereoselective conversion to a corresponding [enatiomer] enantiomer of I are also disclosed.

We claim: 
     
       1. A compound selected from substantially pure (+)-1-(3-Dimethylaminopropyl)-1-(4'- fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile and non-toxic acid addition salts thereof. 
     
     
       2. A compound of claim 1 being .Iadd.the .Iaddend.pamoic acid salt of substantially pure (+)-1-(3-dimethylaminopropyl)-1-(4'-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile. 
     
     
       3. A pharmaceutical composition in unit dosage form comprising a pharmaceutically acceptable diluent or adjuvant and, as an active ingredient, a compound as defined in claim 1. 
     
     
       4. A pharmaceutical composition in unit dosage form comprising a pharmaceutically acceptable diluent or adjuvant and, as an active ingredient, the compound of claim 2. 
     
     
       5. A pharmaceutical composition in unit dosage form, according to claim 3, wherein the active ingredient is present in an amount from 0.1 to 100 milligram per unit dose. 
     
     
       6. A pharmaceutical composition in unit dosage form, according to claim 4, wherein the active ingredient is present in an amount from 0.1 to 100 milligram per unit dose. 
     
     
       7. A method for the alleviation of depression in a living animal body subject thereto which comprises the step of administering to the living animal body an amount of a compound of claim 1 which is effective for said purpose. 
     
     
       8. A method for the alleviation of depression in a living animal body subject thereto which comprises the step of administering to the living animal body an amount of a compound of claim 2 which is effective for said purpose. 
     
     
       9. Method of claim .[.10.]. .Iadd.7 .Iaddend.wherein the compound is administered in the form of a pharmaceutical composition thereof. 
     
     
       10. Method of claim 8 wherein the compound is administered in the form of a pharmaceutical composition thereof. 
     
     
       11. A method for the preparation of a compound as defined in claim 1, which comprises, converting substantially, pure .[.(+)-4-(4-dimethylamino)-1-(4'-fluorophenyl)-1-(hydroxybutyl)-3-(hydroxymethyl)-benzonitrile.]. .Iadd.(-)-4-[4-(dimethylamino)-1-(4'-fluorophenyl)-1-hydroxy-1-butyl]-3-(hydroxymethyl)-benzonitrile .Iaddend.or a .[.monomester.]. .Iadd.monoester .Iaddend.thereof in a stereoselective way to substantially pure (+)-1-(3-dimethylaminopropyl)-1-(4'-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile which is isolated as such or as a non-toxic acid addition salt thereof. 
     
     
       12. A compound of the formula .Iadd.(31)-Enantiomer of the compound 4-[4-(dimethylamino)-1-(4'-fluorophenyl)-1-hydroxy-1-butyl]-3-(hydroxymethyl)-benzonitrile or an ester of said (-)enantiomer, which has the formula .Iaddend. ##STR6## wherein R is hydrogen or represents a group completing a labile ester.