Ammonium Chloride → 2-(1-Phenyl-cyclopentyl)-acetamidine HCl salt

To a stirred suspension of NH4Cl (5.9 g, 111.97 mmol) in toluene (200 mL) was added trimethylaluminium (2 Min toluene) (56 mL, 111.96 mmol) at 5° C. The reaction mixture was allowed to warm up to room temperature and stirred for 2 h. A solution of [1-(4-chlorophenyl)-cyclopentyl]-acetonitrile (321) (8.2 g, 37.32 mmol) in toluene (20 mL) was added to the reaction mixture at room temperature and the reaction mixture was heated at 80° C. for 14 h. After completion of the reaction, the reaction mixture was quenched with a suspension of silica gel (32 g) in chloroform (32 mL) at 0° C. The quenched mixture was stirred for 30 min at room temperature and filtered through a pad of celite. The residue was washed with methanol (5×50 mL) and the combined filtrate was concentrated. The residue was stirred in 10% methanol in dichloromethane (150 mL) and the resulting white solid was discarded by filtration and the filtrate was concentrated to get 2-(1-phenyl-cyclopentyl)-acetamidine, hydrochloride (322) (7 g, 79%, crude) as a yellow gummy oil.

1. temperaturethe reaction mixture was heated at 80° C. for 14 h
2. customAfter completion of the reaction
3. customthe reaction mixture was quenched with a suspension of silica gel (32 g) in chloroform (32 mL) at 0° C
4. stirringThe quenched mixture was stirred for 30 min at room temperature
5. filtrationfiltered through a pad of celite
6. washThe residue was washed with methanol (5×50 mL)
7. concentrationthe combined filtrate was concentrated
8. stirringThe residue was stirred in 10% methanol in dichloromethane (150 mL)
9. filtrationthe resulting white solid was discarded by filtration
10. concentrationthe filtrate was concentrated

ORD record

ord-a609d477b864422b8fa9f295162ec893

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09045486B2