(r)-6-(dimethylamino)-4,4-diphenylheptan-3-one

A process to produce (R)-6-(dimethylamino)-4,4-diphenylheptan-3-one wherein the process includes steps of:

• i) preparing a charge mixture comprising a solution containing polar aprotic solvents, a base, and an organic salt;
• ii) heating the charge mixture at a temperature ranging from 50° C. to 55° C. to allow reaction and effect formation of 4-(dimethylamino)-2,2-diphenylpentanitrile;
• iii) separating the 4-(dimethylamino)-2,2-diphenylpentanitrile from unreacted mixture;
• iv) dissolving the 4-(dimethylamino)-2,2-diphenylpentanitrile in an organic solvent;
• v) heating the organic solvent mixture containing 4-(dimethylamino)-2,2-diphenylpentanitrile to a temperature ranging from 50° C. to 55° C. for at least 30 minutes;
• vi) cooling at a temperature ranging from 40° C. to 45° C. to form solid 4-(dimethylamino)-2,2-diphenylpentanitrile;
• vii) conducting filtration to separate the solid form 4-(dimethylamino)-2,2-diphenylpentanitrile form the mixture;
• viii) washing the solid form 4-(dimethylamino)-2,2-diphenylpentanitrile with an organic solvent;
• ix) removing the solvent to leave pure crystalized 4-(dimethylamino)-2,2-diphenylpentanitrile;
• x) conducting alkylation of pure crystalized 4-(dimethylamino)-2,2-diphenylpentanitrile obtained in step (ix) to effect formation of 4-(dimethylamino)-2,2-diphenylpentanitrile ethyl magnesium halide complex;
• xi) conducting hydrolysis of 4-(dimethylamino)-2,2-diphenylpentanitrile ethyl magnesium halide complex obtained in step (x) to produce 6-(dimethylamino)-4,4-diphenylheptan-3-one;
• xii) mixing pure crystalized 6-(dimethylamino)-4,4-diphenylheptan-3-one obtained in step xi) with a charge of mixture comprising absolute alcohol, an aliquot of demineralised water, and a bromocamphor salt;
• xiii) heating the charge mixture to a temperature ranging from 50° C. to 55° C. to allow reaction and effect resolution of 6-(dimethylamino)-4,4-diphenylheptan-3-one into (R)-6-(dimethylamino)-4,4-diphenylheptan-3-one;
• xiv) cooling the mixture at a temperature ranging from 0° C. to 5° C.;
• xv) conducting filtration;
• xvi) washing with demineralised water;
• xvii) adding a base to the mixture;
• xviii) stirring the mixture for at least 480 minutes at a temperature ranging from 25° C. to 30° C.;
• xix) cooling the mixture at a temperature ranging from 5° C. to 10° C.;
• xx) conducting filtration to separate (R)-6-(dimethylamino)-4,4-diphenylheptan-3-one from the mixture;
• xxi) dissolving (R)-6-(dimethylamino)-4,4-diphenylheptan-3-one obtained in step (xx) in a solvent;
• xxii) heating the solvent containing (R)-6-(dimethylamino)-4,4-diphenylheptan-3-one up to a temperature ranging from 50° C. to 55° C.;
• xxiii) stirring solvent containing (R)-6-(dimethylamino)-4,4-diphenylheptan-3-one for at least 60 minutes;
• xxiv) cooling solvent containing (R)-6-(dimethylamino)-4,4-diphenylheptan-3-one at a temperature ranging from 5° C. to 10° C.;
• xxv) stirring the solvent containing the solid (R)-6-(dimethylamino)-4,4-diphenylheptan-3-one for at least 180 minutes to form solid (R)-6-(dimethylamino)-4,4-diphenylheptan-3-one;
• xxvi) conducting filtration to separate solid (R)-6-(dimethylamino)-4,4-diphenylheptan-3-one from the unreacted mixture;
• xxvii) washing the solid (R)-6-(dimethylamino)-4,4-diphenylheptan-3-one using a solvent;
• and;
• xxviii) removing the solvent to leave pure crystalized solid (R)-6-(dimethylamino)-4,4-diphenylheptan-3-one.