Water → tert-Butyl [(1R,2S,5S)-2-amino-5-[(dimethylamino)carbonyl]cyclohexyl]carbamate oxalate

Temperature

35 °C

Oxalic acid (16.24 g) was added to acetonitrile (640 ml) and water (40 ml), and the obtained solution was then heated to approximately 35° C. To this solution, a solution of tert-butyl(1R,2S,5S)-2-amino-5-[(dimethylamino)carbonyl]cyclohexylcarbamate prepared by the above described method in acetonitrile (approximately 640 ml) was added dropwise, and the obtained mixture was then stirred at approximately 35° C. for approximately 1 hour. Thereafter, the reaction solution was cooled to approximately 25° C., and was then stirred for approximately 1 hour. The precipitated crystals were filtered, and were then washed with 7% aqueous acetonitrile (300 ml) to obtain a monohydrate of the title compound (tert-butyl(1R,2S,5S)-2-amino-5-[(dimethylamino) carbonyl]cyclohexylcarbamate oxalate monohydrate). To this monohydrate of the title compound, acetonitrile (560 ml) was added, and the obtained mixture was then heated to approximately 70° C. The reaction mixture was stirred at this temperature for approximately 5 hours, and was then concentrated to approximately 320 ml. Thereafter, acetonitrile (320 ml) was added to the concentrated solution, and the obtained mixture was then cooled to approximately 25° C. The precipitated crystals were filtered and were then washed with acetonitrile (80 ml), followed by drying under reduced pressure, to obtain an anhydride of the title compound (55.74 g, yield: 82%).

1. additionwas added dropwise
2. temperatureThereafter, the reaction solution was cooled to approximately 25° C.
3. stirringwas then stirred for approximately 1 hour
4. filtrationThe precipitated crystals were filtered
5. washwere then washed with 7% aqueous acetonitrile (300 ml)

ORD record

ord-2c952f17cbf14f4aac575dba11311159

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09447118B2