| 主权项 |
1. 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. |
