This patent says enantiopure amphetamines can be had from hydrogenation of (4S,5R)-(-)-4-methyl-5-phenyl-2-oxazolidinone (CAS 16251-45-9) and derivatives.
Dextroamphetamine
A mixture of 6.00 g (33.9 mmol) (4S,5R)-(-)-4-methyl-5-phenyl-2-oxazolidinone, 0.34 g 10% palladium-on-carbon (50% water wet), and 60 mL SDA-3A (a solvent constituting 95% Ethanol and 5% Methanol) was stirred under a hydrogen filled balloon at ambient temperature (approximately 20° C.) until no more oxazolidinone was detected by HPLC, 4 h. The reaction mixture was then filtered through a pad of Celite to remove the catalyst. For the purposes of isolating the free base, a filtered reaction mixture was carefully concentrated under reduced pressure to leave 4.47 g of a crystalline semi-solid, which was found to be a mixture of 96% dextroamphetamine and 4% ethanol by 1H NMR. Some dextroamphetamine was detected in the distillate. Yield=94%. 400 MHz 1H NMR (CDCl3) 7.34-7.20 (m, 5), 3.22-3.17 (m, 1), 2.76-2.72 (d of d, J=13.2 Hz, J'=5.4 Hz, 1), 2.57-2.52 (d of d, J=13.2 Hz, J'=8.1 Hz, 1), 1.16-1.14 (d, J=6.3 Hz, 3).
Methamphetamine
A mixture of 1.00 g (5.23 mmol) (4S,5R)-3,4-dimethyl-5-phenyl-2-oxazolidinone, 0.0530 g 10% palladium-on-carbon (50% water wet), and 10 mL SDA-3A was stirred under a hydrogen filled balloon at ambient temperature overnight. The reaction had no detectable oxazolidinone by HPLC in the morning.
Dextroamphetamine
A mixture of 6.00 g (33.9 mmol) (4S,5R)-(-)-4-methyl-5-phenyl-2-oxazolidinone, 0.34 g 10% palladium-on-carbon (50% water wet), and 60 mL SDA-3A (a solvent constituting 95% Ethanol and 5% Methanol) was stirred under a hydrogen filled balloon at ambient temperature (approximately 20° C.) until no more oxazolidinone was detected by HPLC, 4 h. The reaction mixture was then filtered through a pad of Celite to remove the catalyst. For the purposes of isolating the free base, a filtered reaction mixture was carefully concentrated under reduced pressure to leave 4.47 g of a crystalline semi-solid, which was found to be a mixture of 96% dextroamphetamine and 4% ethanol by 1H NMR. Some dextroamphetamine was detected in the distillate. Yield=94%. 400 MHz 1H NMR (CDCl3) 7.34-7.20 (m, 5), 3.22-3.17 (m, 1), 2.76-2.72 (d of d, J=13.2 Hz, J'=5.4 Hz, 1), 2.57-2.52 (d of d, J=13.2 Hz, J'=8.1 Hz, 1), 1.16-1.14 (d, J=6.3 Hz, 3).
Methamphetamine
A mixture of 1.00 g (5.23 mmol) (4S,5R)-3,4-dimethyl-5-phenyl-2-oxazolidinone, 0.0530 g 10% palladium-on-carbon (50% water wet), and 10 mL SDA-3A was stirred under a hydrogen filled balloon at ambient temperature overnight. The reaction had no detectable oxazolidinone by HPLC in the morning.
OxazolidinoneChiralAuxillaryAlsoMethPrecursor.svg
US2010125146A1.pdf