1,2-diphenylpropan-2-amine

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: By procedures essentially the same as those described in Example 2 and by substituting (-)-1,2-diphenyl-2-propylamine for 1,2-diphenyl-2-propylamine; the corresponding (-)-2-(methylamino)-N-(1,2-diphenyl-1-methylethyl)acetamide hydrochloride, mp. 171°-172.5° C., was prepared.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Racemic 1,2-diphenyl-2-propylamine (86 g, 0.4 mol) was dissolved in 0.5L 95% ethanol, heated to near reflux and added to a solution of (-)-dibenzoyltartaric acid monohydrate (151.9 g, 0.4 mol) in 0.5L 95% ethanol also at reflux. A white solid crystallized immediately. The mixture was refluxed for 5 minutes, then allowed to cool to ambient temperature. The solid was collected by filtration and dried to give 86.2 g [α]D =-94.2° (C=0.5, CH3OH). The filtrate was saved. The solid was suspended in 0.9L of 95% ethanol, stirred and heated to reflux for 1 hour, allowed to cool to ambient temperature and the white solid collected by filtration and vacuum dried at 80° C. for 8 hours to give 60.2 g of (-)-1,2-diphenyl-2-propylamine (-)-dibenzoyl tartrate, mp 194°-195° C., [α]D =-96.0° (C=0.5, CH3OH). 5.0 g of this salt was dissolved in 250 ml CHCl3 and 200 ml 5% NH4OH shaken vigorously, the layers separated and the organic phase washed with 3×200 ml 5% NH4OH, 2×200 ml H2O and dried over MgSO4. The solvent was evaporated to give 1.75 g of (-)-1,2-diphenyl- 2-propylamine as an oil. The maleate salt was prepared by dissolving this oil in 25 ml of ethyl acetate and adding the solution to a hot solution of maleic acid (1.02 g, 8.87 mmol) in 50 ml of 3/1 ethyl acetate/isopropanol. Upon cooling a white solid crystallized, which was collected by filtration and vacuum dried to give 2.05 g of (-)-1,2-diphenyl-2-propylamine maleate, mp. 176°-177° C., [α]D =-27.4° (C=1, CH3OH). heated to near reflux at reflux A white solid crystallized immediately The mixture was refluxed for 5 minutes The solid was collected by filtration dried to give 86.2 g [α]D =-94.2° (C=0.5, CH3OH) heated to reflux for 1 hour to cool to ambient temperature the white solid collected by filtration and vacuum dried at 80° C. for 8 hours

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Racemic 1,2-diphenyl-2-propylamine (86 g, 0.4 mol) was dissolved in 0.5L 95% ethanol, heated to near reflux and added to a solution of (-)-dibenzoyltartaric acid monohydrate (151.9 g, 0.4 mol) in 0.5L 95% ethanol also at reflux. A white solid crystallized immediately. The mixture was refluxed for 5 minutes, then allowed to cool to ambient temperature. The solid was collected by filtration and dried to give 86.2 g [α]D =-94.2° (C=0.5, CH3OH). The filtrate was saved. The solid was suspended in 0.9L of 95% ethanol, stirred and heated to reflux for 1 hour, allowed to cool to ambient temperature and the white solid collected by filtration and vacuum dried at 80° C. for 8 hours to give 60.2 g of (-)-1,2-diphenyl-2-propylamine (-)-dibenzoyl tartrate, mp 194°-195° C., [α]D =-96.0° (C=0.5, CH3OH). 5.0 g of this salt was dissolved in 250 ml CHCl3 and 200 ml 5% NH4OH shaken vigorously, the layers separated and the organic phase washed with 3×200 ml 5% NH4OH, 2×200 ml H2O and dried over MgSO4. The solvent was evaporated to give 1.75 g of (-)-1,2-diphenyl- 2-propylamine as an oil. The maleate salt was prepared by dissolving this oil in 25 ml of ethyl acetate and adding the solution to a hot solution of maleic acid (1.02 g, 8.87 mmol) in 50 ml of 3/1 ethyl acetate/isopropanol. Upon cooling a white solid crystallized, which was collected by filtration and vacuum dried to give 2.05 g of (-)-1,2-diphenyl-2-propylamine maleate, mp. 176°-177° C., [α]D =-27.4° (C=1, CH3OH). heated to near reflux at reflux A white solid crystallized immediately The mixture was refluxed for 5 minutes The solid was collected by filtration dried to give 86.2 g [α]D =-94.2° (C=0.5, CH3OH) heated to reflux for 1 hour to cool to ambient temperature the white solid collected by filtration and vacuum dried at 80° C. for 8 hours

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Racemic 1,2-diphenyl-2-propylamine (86 g, 0.4 mol) was dissolved in 0.5 L 95% ethanol, heated to near reflux and added to a solution of (-)-dibenzoyltartaric acid monohydrate (151.9 g, 0.4 mol) in 0.5 L 95% ethanol also at reflux. A white solid crystallized immediately. The mixture was refluxed for 5 minutes, then allowed to cool to ambient temperature. The solid was collected by filtration and dried to give 86.2 g, [α]D =94.2° (C=0.5, CH3OH). The filtrate was saved. The solid was suspended in 0.9 L of 95% ethanol, stirred and heated to reflux for 1 hour, allowed to cool to ambient temperature and the white solid collected by filtration and vacuum dried at 80° C. for 8 hours to give 60.2 g of (-)-1,2-diphenyl-2-propylamine (-)-dibenzoyl tartrate, mp 194°-195° C. [α]D =-96.0° (C=0.5, CH3OH). 5.0 g of this salt was dissolved in 250 ml CHCl3 and 200 ml 5% NH4OH shaken vigorously, the layers separated and the organic phase washed with 3×200 ml 5% NH4OH, 2×200 ml H2O and dried over MgSO4. The solvent was evaporated to give 1.75 g of (-)-1,2-diphenyl-2-propylamine as an oil. The maleate salt was prepared by dissolving this oil in 25 ml of ethyl acetate and adding the solution to a hot solution of maleic acid (1.02 g, 8.87 mmol) in 50 ml of 3/1 ethyl acetate/isopropanol. Upon cooling a white solid crystallized, which was collected by filtration and vacuum dried to give 2.05 g of (-)-1,2-diphenyl-2-propylamine maleate, mp 176°-177° C., [α]D =-27.4° (C=1, CH3OH). heated to near reflux at reflux A white solid crystallized immediately The mixture was refluxed for 5 minutes The solid was collected by filtration dried to give 86.2 g, [α]D =94.2° (C=0.5, CH3OH) heated to reflux for 1 hour to cool to ambient temperature the white solid collected by filtration and vacuum dried at 80° C. for 8 hours

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Racemic 1,2-diphenyl-2-propylamine (86 g, 0.4 mol) was dissolved in 0.5 L 95% ethanol, heated to near reflux and added to a solution of (-)-dibenzoyltartaric acid monohydrate (151.9 g, 0.4 mol) in 0.5 L 95% ethanol also at reflux. A white solid crystallized immediately. The mixture was refluxed for 5 minutes, then allowed to cool to ambient temperature. The solid was collected by filtration and dried to give 86.2 g, [α]D =94.2° (C=0.5, CH3OH). The filtrate was saved. The solid was suspended in 0.9 L of 95% ethanol, stirred and heated to reflux for 1 hour, allowed to cool to ambient temperature and the white solid collected by filtration and vacuum dried at 80° C. for 8 hours to give 60.2 g of (-)-1,2-diphenyl-2-propylamine (-)-dibenzoyl tartrate, mp 194°-195° C. [α]D =-96.0° (C=0.5, CH3OH). 5.0 g of this salt was dissolved in 250 ml CHCl3 and 200 ml 5% NH4OH shaken vigorously, the layers separated and the organic phase washed with 3×200 ml 5% NH4OH, 2×200 ml H2O and dried over MgSO4. The solvent was evaporated to give 1.75 g of (-)-1,2-diphenyl-2-propylamine as an oil. The maleate salt was prepared by dissolving this oil in 25 ml of ethyl acetate and adding the solution to a hot solution of maleic acid (1.02 g, 8.87 mmol) in 50 ml of 3/1 ethyl acetate/isopropanol. Upon cooling a white solid crystallized, which was collected by filtration and vacuum dried to give 2.05 g of (-)-1,2-diphenyl-2-propylamine maleate, mp 176°-177° C., [α]D =-27.4° (C=1, CH3OH). heated to near reflux at reflux A white solid crystallized immediately The mixture was refluxed for 5 minutes The solid was collected by filtration dried to give 86.2 g, [α]D =94.2° (C=0.5, CH3OH) heated to reflux for 1 hour to cool to ambient temperature the white solid collected by filtration and vacuum dried at 80° C. for 8 hours

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Racemic 1,2-diphenyl-2-propylamine (86 g, 0.4 mol) was dissolved in 0.5 L 95% ethanol, heated to near reflux and added to a solution of (-)-dibenzoyltartaric acid monohydrate (151.9 g, 0.4 mol) in 0.5 L 95% ethanol also at reflux. A white solid crystallized immediately. The mixture was refluxed for 5 minutes, then allowed to cool to ambient temperature. The solid was collected by filtration and dried to give 86.2 g, [α]D =-94.2° (C=0.5, CH3OH). The filtrate was saved. The solid was suspended in 0.9 L of 95% ethanol, stirred and heated to reflux for 1 hour, allowed to cool to ambient temperature and the white solid collected by filtration and vacuum dried at 80° C. for 8 hours to give 60.2 g of (-)-1,2-diphenyl-2-propylamine (-)-dibenzoyl tartrate, mp 194°-195° C., [α]D =-96.0° (C=0.5, CH3OH). 5.0 g of this salt was dissolved in 250 ml CHCl3 and 200 ml 5% NH4OH shaken vigorously, the layers separated and the organic phase washed with 3×200 ml 5% NH4OH, 2×200 ml H2O and dried over MgSO4. The solvent was evaporated to give 1.75 g of (-)-1,2-diphenyl-2-propylamine as an oil. The maleate salt was prepared by dissolving this oil in 25 ml of ethyl acetate and adding the solution to a hot solution of maleic acid (1.02 g, 8.87 mmol) in 50 ml of 3/1 ethyl acetate/isopropanol. Upon cooling a white solid crystallized, which was collected by filtration and vacuum dried to give 2.05 g of (-)-1,2-diphenyl-2-propylamine maleate, mp 176°-177° C., [α]D =-27.4° (C=1, CH3OH). heated to near reflux at reflux A white solid crystallized immediately The mixture was refluxed for 5 minutes The solid was collected by filtration dried to give 86.2 g, [α]D =-94.2° (C=0.5, CH3OH) heated to reflux for 1 hour to cool to ambient temperature the white solid collected by filtration and vacuum dried at 80° C. for 8 hours

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 1,2-diphenyl-2-propylamine (21.0 g, 0,085 mol) in chloroform (500 ml) under nitrogen was added N-CBZ-glycine (23.0 g, 0.11 mol), and then a solution of dicyclohexylcarbodiimide (20.6 g, 0.1 mol) in chloroform (100 ml) and the mixture stirred for 14 hours. The precipitated solid was removed by filtration and the solvent evaporated. The residue was dissolved in methylene chloride (500 ml), filtered and evaporated to a yellow oil. This was treated with ether (700 ml) and 500 ml of ice cold water, basified with 5 ml of 50% NaOH, the layers shaken and separated. The ether layer was washed with water (2×125 ml), dried and evaporated to an oil, 33.5 g. This was dissolved in methanol (500 ml) and 10% HCl (50 ml) and hydrogenated at 40 psi in a Parr apparatus over 3.0 g of 10% Pd/C catalyst for 4 hours. The catalyst was removed by filtration, and the solvent evaporated to a white solid. This was dissolved in 80 ml of hot methanol and treated with 200 ml of ether. Upon cooling a solid crystallised which was recrystallised from 100 ml of isopropanol and 100 ml of methanol to give 8.4 g of 2-amino-N-(1,2-diphenyl-1-methylethyl)acetamide hydrochloride which, after vacuum drying at 80° C. for 24 hours, had mp 253°-254° C. The precipitated solid was removed by filtration the solvent evaporated The residue was dissolved in methylene chloride (500 ml) filtered evaporated to a yellow oil This was treated with ether (700 ml) and 500 ml of ice cold water separated The ether layer was washed with water (2×125 ml) dried evaporated to an oil, 33.5 g This was dissolved in methanol (500 ml) The catalyst was removed by filtration the solvent evaporated to a white solid This was dissolved in 80 ml of hot methanol treated with 200 ml of ether Upon cooling a solid crystallised which was recrystallised from 100 ml of isopropanol and 100 ml of methanol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 1,2-diphenyl-2-propylamine (21.0 g, 0.085 mol) in chloroform (500 ml) under nitrogen was added N-CBZ-glycine (23.0 g, 0.11 mol), and then a solution of dicyclohexylcarbodiimide (20.6 g, 0.1 mol) inchloroform (100 ml) and the mixture stirred for 14 hours. The precipitated solid was removed by filtration and the solvent evaporated. The residue was dissolved in methylene chloride (500 ml), filtered and evaporated to ayellow oil. This was treated with ether (700 ml) and 500 ml of ice cold water, basified with 5 ml of 50% NaOH, the layers shaken and separated. The ether layer was washed with water (2×125 ml), dried and evaporated to an oil, 33.5 g. This was dissolved in methanol (500 ml) and 10% HCl (50 ml) and hydrogenated at 40psi in a Parr apparatus over 3.0 g of 10% Pd/C catalyst for 4 hours. The catalyst was removed by filtration, and the solvent evaporated to a white solid. This was dissolved in 80 ml of hot methanol and treated with 200 ml of ether. Upon cooling a solid crystallised which was recrystallised from 100 ml of isopropanol and 100 ml of methanol to give 8.4 g of 2-amino-N-(1,2-diphenyl-1-methylethyl)acetamide hydrochloride which, aftervacuum drying at 80° C. for 24 hours, had mp 253°-254° C. The precipitated solid was removed by filtration the solvent evaporated The residue was dissolved in methylene chloride (500 ml) filtered evaporated This was treated with ether (700 ml) and 500 ml of ice cold water separated The ether layer was washed with water (2×125 ml) dried evaporated to an oil, 33.5 g This was dissolved in methanol (500 ml) The catalyst was removed by filtration the solvent evaporated to a white solid This was dissolved in 80 ml of hot methanol treated with 200 ml of ether Upon cooling a solid crystallised which was recrystallised from 100 ml of isopropanol and 100 ml of methanol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 1,2-diphenyl-2-propylamine (21.0 g, 0.085 mol) in chloroform (500 ml) under nitrogen was added N-CBZ-glycine (23.0 g, 0.11 mol), and then a solution of dicyclohexylcarbodiimide (20.6 g, 0.1 mol) in chloroform (100 ml) and the mixture stirred for 14 hours. The precipitated solid was removed by filtration and the solvent evaporated. The residue was dissolved in methylene chloride (500 ml), filtered and evaporated to a yellow oil. This was treated with ether (700 ml) and 500 ml of ice cold water, basified with 5 ml of 50% NaOH, the layers shaken and separated. The ether layer was washed with water (2×125 ml), dried and evaporated to an oil, 33.5 g. This was dissolved in methanol (500 ml) and 10% HCl (50 ml) and hydrogenated at 40 psi in a Parr apparatus over 3.0 g of 10% Pd/C catalyst for 4 hours. The catalyst was removed by filtration, and the solvent evaporated to a white solid. This was dissolved in 80 ml of hot methanol and treated with 200 ml of ether. Upon cooling a solid crystallised which was recrystallised from 100 ml of isopropanol and 100 ml of methanol to give 8.4 g of 2-amino-N-(1,2-diphenyl-1-methylethyl)acetamide hydrochloride which, after vacuum drying at 80 ° C. for 24 hours, had mp 253°-254° C. The precipitated solid was removed by filtration the solvent evaporated The residue was dissolved in methylene chloride (500 ml) filtered evaporated to a yellow oil This was treated with ether (700 ml) and 500 ml of ice cold water separated The ether layer was washed with water (2×125 ml) dried evaporated to an oil, 33.5 g This was dissolved in methanol (500 ml) The catalyst was removed by filtration the solvent evaporated to a white solid This was dissolved in 80 ml of hot methanol treated with 200 ml of ether Upon cooling a solid crystallised which was recrystallised from 100 ml of isopropanol and 100 ml of methanol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 1,2-diphenyl-2-propylamine (21.0 g, 0.085 mol) in chloroform (500 ml) under nitrogen was added N-CBZ-glycine (23.0 g, 0.11 mol), and then a solution of dicyclohexylcarbodiimide (20.6 g, 0.1 mol) in chloroform (100 ml) and the mixture stirred for 14 hours. The precipitated solid was removed by filtration and the solvent evaporated. The residue was dissolved in methylene chloride (500 ml), filtered and evaporated to a yellow oil. This was treated with ether (700 ml) and 500 ml of ice cold water, basified with 5 ml of 50% NaOH, the layers shaken and separated. The ether layer was washed with water (2×125 ml), dried and evaporated to an oil, 33.5 g. This was dissolved in methanol (500 ml) and 10% HCl (50 ml) and hydrogenated at 40 psi in a Parr apparatus over 3.0 g of 10% Pd/C catalyst for 4 hours. The catalyst was removed by filtration, and the solvent evaporated to a white solid. This was dissolved in 80 ml of hot methanol and treated with 200 ml of ether. Upon cooling a solid crystallised which was recrystallised from 100 ml of isopropanol and 100 ml of methanol to give 8.4 g of 2-amino-N-(1,2-diphenyl-1-methylethyl)acetamide hydrochloride which, after vacuum drying at 80° C. for 24 hours, had mp 253°-254° C. The precipitated solid was removed by filtration the solvent evaporated The residue was dissolved in methylene chloride (500 ml) filtered evaporated to a yellow oil This was treated with ether (700 ml) and 500 ml of ice cold water separated The ether layer was washed with water (2×125 ml) dried evaporated to an oil, 33.5 g This was dissolved in methanol (500 ml) The catalyst was removed by filtration the solvent evaporated to a white solid This was dissolved in 80 ml of hot methanol treated with 200 ml of ether Upon cooling a solid crystallised which was recrystallised from 100 ml of isopropanol and 100 ml of methanol