Hydrochloric Acid → 1-Cyclobutyl-[1,4]diazepane

Temperature

22.5 °C

To a stirred solution of tert-butyl 4-cyclobutyl-1,4-diazepane-1-carboxylate (6.1 g, 23.98 mmol) in DCM (70 ml) at 20 to 25° C. was added a solution of 4M HCl in dioxane (30 ml, 120 mmol) dropwise. The resulting mixture was stirred at 20 to 25° C. for ca. 2 h. MeOH (6 ml) was added and the resulting mixture stirred at 20 to 25° C. for 1 to 2 days. The solvent was removed in vacuo and the resulting gummy residue slurried in ether (100 ml) for 0.5 h. The solvent was evaporated and the residue slurried in ether/MeOH (10:1, 66 ml). The resulting white solid was collected by filtration, suspended in DCM (150 ml) and treated with 2M NaOH. The aqueous phase was extracted with DCM until complete transfer of product in the organic layer, as monitored by TLC analysis (eluent, DCM/MeOH/conc.NH3 (90:10:1); stain, PMA) was achieved. The combined organic phases were dried (Na2SO4), filtered and concentrated in vacuo to provide the title compound as orange oil (2.67 g, 73%).

1. stirringthe resulting mixture stirred at 20 to 25° C. for 1 to 2 days
2. customThe solvent was removed in vacuo
3. waitthe resulting gummy residue slurried in ether (100 ml) for 0.5 h
4. customThe solvent was evaporated
5. filtrationThe resulting white solid was collected by filtration
6. additiontreated with 2M NaOH
7. extractionThe aqueous phase was extracted with DCM until complete transfer of product in the organic layer
8. dry with materialThe combined organic phases were dried (Na2SO4)
9. filtrationfiltered
10. concentrationconcentrated in vacuo

ORD record

ord-b91330c095ef4fd5bbb10d30dd1d024f

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08691804B2