Hydrochloric Acid → 1H-Indole-5-methanamine, 2-(trifluoromethyl)-, hydrochloride (1:1)

Temperature

40 °C

2-(trifluoromethyl)-1H-indole-5-carbonitrile (Intermediate 3A, 25 g), PtO2.H2O (3%, 750 mg) and MeOH (175 mL) were added to a hydrogenation flask. 4M HCl in dioxane (89 mL) was added and the reaction vessel is purged with N2 and then H2. The mixture was hydrogenated at 60 psi of H2 and 17-23° C. for 24 hrs. The mixture was filtered through celite and then through a 0.2 μm PTFE filter. MP-TMT resin (15 wt %) was then added and the slurry was stirred for 3 hrs at 40° C., cooled to 17-23° C., and then filtered through a pad of celite. The celite pad and resin were washed with MeOH (100 mL). The solution was concentrated to a minimum by vacuum distillation and n-propanol (200 mL) was added and concentrated to a minimum. Toluene (200 mL) was added and then cyclohexane (75 mL) and the slurry was allowed to stir for 2 hrs at 17-23° C. The mixture was then cooled to 0-5° C. and allowed to stir for 2 hrs. The solid was filtered and washed with toluene to give the title compound (25.3 g);

1. customthe reaction vessel is purged with N2
2. filtrationThe mixture was filtered through celite
3. filtrationthrough a 0.2 μm PTFE filter
4. additionMP-TMT resin (15 wt %) was then added
5. temperaturecooled to 17-23° C.
6. filtrationfiltered through a pad of celite
7. washThe celite pad and resin were washed with MeOH (100 mL)
8. concentrationThe solution was concentrated to a minimum by vacuum distillation and n-propanol (200 mL)
9. additionwas added
10. concentrationconcentrated to a minimum
11. additionToluene (200 mL) was added
12. stirringto stir for 2 hrs at 17-23° C
13. temperatureThe mixture was then cooled to 0-5° C.
14. stirringto stir for 2 hrs
15. filtrationThe solid was filtered
16. washwashed with toluene

ORD record

ord-c745c45081a34c97a74a9af1869d5ccf

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08283365B2