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(R)-6-(dimethylamino)-4,4-diphenylheptan-3-one and a process to produce thereof.
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.
2. The process as claimed in claim 1 wherein the polar aprotic solvents in step (i) are diphenylacetonitrile and dimethylformamide.
3. The process as claimed in claim 1 wherein the base in step (i) is sodium hydroxide.
4. The process as claimed in claim 1 wherein the organic salt is aziridine salt.
5. The process as claimed in claim 1 wherein the organic solvent in step (iv) is hexane.
6. The process as claimed in claim 1 wherein step (vii) is conducted by vacuum drying at a temperature ranging from 40° C. to 45° C.
7. The process as claimed in claim 1 wherein step (viii) is conducted by vacuum drying at a temperature ranging from 35° C. to 40° C.
8. The process as claimed in claim 1 wherein the base in step (xvii) is 40% sodium hydroxide.
9. The process as claimed in claim 1 wherein the solvent in step (xxvii) is acetone.
10. The process as claimed in claim 2 wherein ratio of diphenylacetonitrile to dimethylformamide is 1:1.
11. The process as claimed in claim 1 wherein step (x) further includes steps of:
i) preparing a charge mixture is comprising ether, an ethyl magnesium halide and a solution containing pure crystalized 4-(dimethylamino)-2,2-diphenylpentanitrile in xylene;
ii) heating the charge mixture at a temperature ranging from 40° C. to 80° C. to allow reaction and to effect formation of 4-(dimethylamino)-2,2-diphenylpentanitrile ethyl magnesium halide complex;
iii) conducting distillation on the mixture at 80° C.; and
iv) conducting reflux at a temperature ranging from 110° C. to 115° C. to form pure 4-(dimethylamino)-2,2-diphenylpentanitrile ethyl magnesium halide complex.
12. The process as claimed in claim 8 wherein the ethyl magnesium halide is ethyl magnesium bromide.
13. The process as claimed in claim 8 wherein ratio of 4-(dimethylamino)-2,2-diphenylpentanitrile to xylene is 1:2.
14. The process as claimed in claim 1 wherein step (xi) further includes steps of:
i) preparing a charge mixture comprising of pure 4-(dimethylamino)-2,2 diphenylpentanitrile ethyl magnesium halide complex, concentrated hydrochloric acid and an aliquot of demineralised water to effect formation of 6-(dimethylamino)-4,4-diphenylheptan-3-one;
ii) conducting distillation at 80° C.;
iii) conducting cooling at a temperature ranging from 20° C. to 25° to effect formation of solid form 6-(dimethylamino)-4,4-diphenylheptan-3-one;
iv) conducting filtration to separate the solid form 6-(dimethylamino)-4,4-diphenylheptan-3-one;
v) washing the solid form 6-(dimethylamino)-4,4-diphenylheptan-3-one with an acid;
vi) dissolving the solid form 6-(dimethylamino)-4,4-diphenylheptan-3-one in a solvent; and;
vii) removing the solvent to leave pure crystalized 6-(dimethylamino)-4,4 diphenylheptan-3-one.
15. The process as claimed in claim 11 wherein the acid in step (v) is 50% v/v hydrochloric acid.
16. The process as claimed in claim 11 wherein the solvent is methanol.
17. The process as claimed in claim 11 wherein step (vii) is conducted by vacuum drying at a temperature ranging from 50° C. to 55° C.
18. A process to produce (R)-6-(dimethylamino)-4,4-diphenylheptan-3-one wherein the process includes steps of:
i) preparing a charge mixture is comprising ether, an ethyl magnesium halide and a solution containing pure crystalized 4-(dimethylamino)-2,2-diphenylpentanitrile in xylene;
ii) heating the charge mixture at a temperature ranging from 40° C. to 80° C. to allow reaction and to effect formation of 4-(dimethylamino)-2,2-diphenylpentanitrile ethyl magnesium halide complex;
iii) conducting distillation on the mixture at 80° C.;
iv) conducting reflux at a temperature ranging from 110° C. to 115° C. to form pure 4-(dimethylamino)-2,2-diphenylpentanitrile ethyl magnesium halide complex;
v) mixing the 4-(dimethylamino)-2,2diphenylpentanitrile ethyl magnesium halide complex with a charge mixture comprising concentrated hydrochloric acid and an aliquot of demineralised water to effect formation of 6-(dimethylamino)-4,4-diphenylheptan-3-one;
vi) conducting distillation at 80° C.;
vii) conducting cooling at a temperature ranging from 20° C. to 25° to effect formation of solid form 6-(dimethylamino)-4,4-diphenylheptan-3-one;
viii) conducting filtration to separate the solid form 6-(dimethylamino)-4,4-diphenylheptan-3-one;
ix) washing the solid form 6-(dimethylamino)-4,4-diphenylheptan-3-one with an acid;
x) dissolving the solid form 6-(dimethylamino)-4,4-diphenylheptan-3-one in a solvent;
xi) removing the solvent to leave pure crystalized 6-(dimethylamino)-4,4diphenylheptan-3-one;
xii) mixing pure crystalized 6-(dimethylamino)-4,4-diphenylheptan-3-one 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 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 (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.