(1R)-N-benzyl-1-phenylethanamine

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of N-benzyl-(R)-α-methylbenzylamine (97.5 g, 462 mmol) in THF (750 mL) at 0° C. was added n-butyllithium (2.5M in hexanes; 178.5 mL, 446 mmol). The dark violet solution was stirred at 0° C. for 20 minutes, cooled to −78° C., and the ester 16-3 (63.7 g, 308 mmol) in THF (250 mL) was added over 60 minutes. The resulting solution was stirred at −78° C. for 1 hr, then cannulated into saturated NH4Cl and extracted with EtOAc, washed with water then brine, dried and concentrated in vacuo to give an oil. Column chromatography (silica gel; hexane/EtOAc 9:1 then 4:1) gave 16-4 as an oil contaminated with N-benzyl-(R)-α-methylbenzylamine. This oil was taken up in 5% AcOH in water and extracted with diethyl ether (4×). The organic layers were dried over MgSO4 and the solvent removed to give the title compound 16-4. cooled to −78° C. The resulting solution was stirred at −78° C. for 1 hr extracted with EtOAc washed with water brine, dried concentrated in vacuo to give an oil

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of N-benzyl-α-(R)-methylbenzylamine (1.32 g, 6.30 mmol) in THF (25 mL) at 0° C. was treated with n-BuLi (2.52 mL of a 2.5 M soln in hexanes). The resulting solution was stirred at 0° C. for 30 min and then cooled to −78° C. A solution of acrylate 6-4 (0.681 g, 3.15 mmol) in THF (5 mL) was added. After stirring for 15 min at −78° C., satd. aq. NH4Cl soln (5 mL) was added and the cold bath removed. The mixture was warmed to room temperature, and extracted with Et2O (2×40 mL). The combined organic extracts were washed with brine (30 mL), dried over MgSO4, filtered, and concentrated. The residue was purified by flash chromatography (10% ethyl acetate/hexanes) to give the β-aminoester 6-5 as a yellow oil. cooled to −78° C After stirring for 15 min at −78° C. the cold bath removed The mixture was warmed to room temperature extracted with Et2O (2×40 mL) The combined organic extracts were washed with brine (30 mL) dried over MgSO4 filtered concentrated The residue was purified by flash chromatography (10% ethyl acetate/hexanes)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of N-benzyl-α-(R)-methylbenzylamine (0.82 g, 3.87 mmol) in THF (25 mL) at 0° C. was treated with n-BuLi (1.6 mL of a 2.5 M soln in hexanes). The resulting solution was stirred at 0° C. for 30 min and then cooled to -78° C. A solution of acrylate 20-5 (0.485 g, 1.76 mmol) in THF (5 mL) was added. After stirring for 15 min at -78° C., satd aq NH4Cl soln (5 mL) was added and the cold bath removed. The mixture was warmed to room temperature, and extracted with Et2O (2×40 mL). The combined organic extracts were washed with brine (30 mL), dried over MgSO4, filtered, and concentrated. The residue was purified by flash chromatography (40% ethyl acetate/hexanes) to give the β-aminoester 20-6 as a yellow oil. cooled to -78° C After stirring for 15 min at -78° C. was added the cold bath removed The mixture was warmed to room temperature extracted with Et2O (2×40 mL) The combined organic extracts were washed with brine (30 mL) dried over MgSO4 filtered concentrated The residue was purified by flash chromatography (40% ethyl acetate/hexanes)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of N-benzyl-(R)-α-methylbenzylamine (97.5 g, 462 mmol) in THF (750 mL) at 0° C. was added n-butyllithium (2.5M in hexanes; 178.5 mL, 446 mmol). The dark violet solution was stirred at 0° C. for 20 minutes, cooled to -78° C. and the ester 19-3 (63.7 g, 308 mmol) in THF (250 mL) was added over 60 minutes. The resulting solution was stirred at -78° C. for 1 hr then cannulated into saturated NH4Cl and extracted with EtOAc, washed with water then brine, dried and concentrated in vacuo to give an oil. Column chromatography (silica gel; hexane/EtOAc, 9:1 then 4:1) gave 19-4 as an oil contaminated with N-benzyl-(R)-α-methylbenzylamine . This oil was taken up in 5% AcOH in water and extracted with diethyl ether (4×). The organic layers were dried over MgSO4 and the solvent removed to give the title compound 19-4. cooled to -78° C. The resulting solution was stirred at -78° C. for 1 hr extracted with EtOAc washed with water brine, dried concentrated in vacuo to give an oil

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a cooled (0° C.) solution of (R)-(+)-N-benzyl-α-methylbenzylamine (4.0 g, 19 mmol) in 50 mL THF was gradually added n-butyllithium (11.3 mL, 2.5 M, 28.2 mmol) over 5 min. The mixture was stirred for 30 min at 0° C. and cooled to -78° C. A solution of 10-2 (2.0 g, 9.4 mmol) in 20 mL THF was gradually added. After stirring for 40 min at -78° C., it was treated with NH4Cl (sat.) at -78° C., warmed to room temperature and extracted three times with EtOAc. The combined organic layers were washed with brine and dried over Na2SO4. After solvent evaporation, the residue was purified using silica gel flash chromatography (EtOAc/hexanes 1:2) to afford the desired product 10-3 as an oil. over 5 min cooled to -78° C After stirring for 40 min at -78° C. warmed to room temperature extracted three times with EtOAc The combined organic layers were washed with brine dried over Na2SO4 After solvent evaporation the residue was purified

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of N-benzyl-α-(R)-methylbenzylamine (1.32 g, 6.30 mmol) in THF (25 mL) at 0° C. was treated with n-BuLi (2.52 mL of a 2.5M soln in hexanes). The resulting solution was stirred at 0° C. for 30 min and then cooled to -78° C. A solution of acrylate 3-4 (0.681 g, 3.15 mmol) in THF (5 mL) was added. After stirring for 15 min at -78° C., satd. aq. NH4Cl soln (5 mL) was added and the cold bath removed. The mixture was warmed to room temperature, and extracted with Et2O (2×40 mL). The combined organic extracts were washed with brine (30 mL), dried over MgSO4, filtered, and concentrated. The residue was purified by flash chromatography (10% ethyl acetate/hexanes) to give the β-aminoester 3-5 as a yellow oil. cooled to -78° C After stirring for 15 min at -78° C. the cold bath removed The mixture was warmed to room temperature extracted with Et2O (2×40 mL) The combined organic extracts were washed with brine (30 mL) dried over MgSO4 filtered concentrated The residue was purified by flash chromatography (10% ethyl acetate/hexanes)

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

Procedure: 412 kg of methanol and 375.7 kg of (R)-1-phenylethylamine (ee=97.1%) are initially taken and 329 kg of benzaldehyde are added dropwise at 24° C. in the course of 120 minutes. Stirring is effected for 6 hours at 24° C., the completeness of the iminization is checked by GC, 6 kg of Pd/C (5% by weight) are added and the crude mixture is hydrogenated with hydrogen for 24 hours at atmospheric pressure. The sample is taken and the composition is investigated by GC analysis. are added

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

Procedure: 412 kg of methanol and 375.7 kg of (R)-1-phenylethylamine (ee=97.1%) are initially taken and 329 kg of benzaldehyde are added dropwise at 24° C. in the course of 120 minutes. Stirring is effected for 6 hours at 24° C., the completeness of the iminization is checked by GC, 6 kg of Pd/C (5% by weight) are added and the crude mixture is hydrogenated with hydrogen for 24 hours at atmospheric pressure. The sample is taken and the composition is investigated by GC analysis. are added

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of N-benzyl-(R)-α-methylbenzylamine (97.5 g, 462 mmol) in THF (750 mL) at 0° C. was added n-butyllithium (2.5M in hexanes; 178.5 mL, 446 mmol). The dark violet solution was stirred at 0° C. for 20 minutes, cooled to -78° C., and the ester 16-3 (63.7 g, 308 mmol) in THF (250 mL) was added over 60 minutes. The resulting solution was stirred at -78° C. for 1 hr, then cannulated into saturated NH4Cl and extracted with EtOAc, washed with water then brine, dried and concentrated in vacuo to give an oil. Column chromatography (silica gel; hexane/EtOAc 9:1 then 4:1) gave 16-4 as an oil contaminated with N-benzyl-(R)-α-methylbenzylamine. This oil was taken up in 5% AcOH in water and extracted with diethyl ether (4×). The organic layers were dried over MgSO4 and the solvent removed to give the title compound 16-4. cooled to -78° C. The resulting solution was stirred at -78° C. for 1 hr extracted with EtOAc washed with water brine, dried concentrated in vacuo to give an oil

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of N-benzyl-(R)-α-methylbenzylamine (97.5 g, 462 mmol) in THF (750 mL) at 0° C. was added n-butyllithium (2.5M in hexanes; 178.5 mL, 446 mmol). The dark violet solution was stirred at 0° C. for 20 minutes, cooled to -78° C., and the ester 16-3 (63.7 g, 308 mmol) in THF (250 mL) was added over 60 minutes. The resulting solution was stirred at -78° C. for 1 hr, then cannulated into saturated NH4Cl and extracted with EtOAc, washed with water then brine, dried and concentrated in vacuo to give an oil. Column chromatography (silica gel; hexane/EtOAc 9:1 then 4:1) gave 16-4 as an oil contaminated with N-benzyl-(R)-α-methylbenzylamine. This oil was taken up in 5% AcOH in water and extracted with diethyl ether (4×). The organic layers were dried over MgSO4 and the solvent removed to give the title compound 16-4. cooled to -78° C. The resulting solution was stirred at -78° C. for 1 hr extracted with EtOAc washed with water brine, dried concentrated in vacuo to give an oil

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of N-benzyl-α-(R)-methylbenzylamine (1.32 g, 6.30 mmol) in THF (25 mL) at 0° C. was treated with n-BuLi (2.52 mL of a 2.5 M soln in hexanes). The resulting solution was stirred at 0° C. for 30 min and then cooled to -78° C. A solution of acrylate 6-4 (0.681 g, 3.15 mmol) in THF (5 mL) was added. After stirring for 15 min at -78° C., satd. aq. NH4Cl soln (5 mL) was added and the cold bath removed. The mixture was warmed to room temperature, and extracted with Et2O (2×40 mL). The combined organic extracts were washed with brine (30 mL), dried over MgSO4, filtered, and concentrated. The residue was purified by flash chromatography (10% ethyl acetate/hexanes) to give the β-aminoester 6-5 as a yellow oil. cooled to -78° C After stirring for 15 min at -78° C. the cold bath removed The mixture was warmed to room temperature extracted with Et2O (2×40 mL) The combined organic extracts were washed with brine (30 mL) dried over MgSO4 filtered concentrated The residue was purified by flash chromatography (10% ethyl acetate/hexanes)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of N-benzyl-(R)-α-methylbenzylamine (97.5 g, 462 mmol) in THF (750 mL) at 0° C. was added n-butyllithium (2.5M in hexanes; 178.5 mL, 446 mmol). The dark violet solution was stirred at 0° C. for 20 minutes, cooled to −78° C., and the ester 1-3 (63.7 g, 308 mmol) in THF (250 mL) was added over 60 minutes. The resulting solution was stirred at −78° C. for 1 hr, then cannulated into saturated NH4Cl and extracted with EtOAc, washed with water, then brine, dried and concentrated in vacuo to give an oil. Column chromatography (silica gel; hexane/EtOAc 9:1 then 4:1) gave 1–4 as an oil contaminated with N-benzyl-(R)-α-methylbenzylamine. This oil was taken up in 5% AcOH in water and extracted with diethyl ether (4×). The organic layers were dried over MgSO4 and the solvent removed to give the title compound 1–4. cooled to −78° C. The resulting solution was stirred at −78° C. for 1 hr extracted with EtOAc washed with water brine, dried concentrated in vacuo to give an oil