General procedure for the synthesis of cis-2-amino-1-cyclopentanecarboxamide from 1-aminocyclopentanecarbonitrile:
1. Preparation of 3-(1-carbamoyl-1-cyclopentylamino)-1-propanesulfonic acid (Compound OT): NaCN (15.34 g, 0.31 mol) and NH4Cl (19.75 g, 0.37 mol) were added to a 250 mL single-necked flask containing 30% NH4OH (120 mL) under vigorous stirring. The corresponding ketones were added dropwise over 20 min at room temperature. The mixture was stirred at room temperature for 3 days and then extracted with dichloromethane (50 mL). The organic layer was separated and dried with anhydrous sodium sulfate for 2 hours. The sodium sulfate was removed by filtration and the solvent was removed under reduced pressure to give crude aminonitrile. Distillation under reduced pressure gave the target product as a colorless oil (14.03 g, 127 mmol, 51% yield).
2. Aminonitrile (41 mmol) was dissolved in 30 mL of CH2Cl2 and added dropwise to 10 g of concentrated sulfuric acid stirred in an ice-water bath, maintaining the internal temperature at 15 °C. The mixture was then stirred in an ice-water bath. The ice bath was then removed and the mixture was heated to 40 °C for 1 hour. The mixture was cooled in the ice water bath and poured into 200 g of crushed ice. The mixture was adjusted to pH 7-8 with 28% NH3 aqueous solution and extracted with EtOAc (3 x 100 mL). The extract was collected, dried (MgSO4) and evaporated to dryness. The crude solid was recrystallized in EtOAc/Hex to give the target product as a white solid (1.36 g, 10.6 mmol, 27% yield).
3. A solution of 1,3-propanesulfonolactone (1 M, 6.30 mL) in toluene was added to a solution of 2-amino-2-methylpropanamide (0.4350 g, 4.26 mmol) in MTBK (7 mL) and ethanol (0.5 mL). The mixture was heated to reflux for 4 hours and then cooled to room temperature. The solid was collected by filtration and rinsed with acetone (2 x 5 mL). The solid was dried in a vacuum oven at 60 °C for 18 h (0.74 g). The solid was recrystallized in ethanol (5 mL) and water (5 mL). After drying, cis-2-amino-1-cyclopentanecarboxamide was obtained as a fine white solid (0.39 g, 2.80 mmol, 45% yield).
