Ammonium Hydroxide → 2-(7-Trifluoromethyl-1H-indol-3-yl)-ethylamine

Temperature

100 °C

Combine in a 500 mL round bottom flask equipped with magnetic stirring, (2-trifluoromethyl-phenyl)-hydrazine (5.0 g, 28.4 mmol) and 4-aminobutyraldehyde dimethyl acetal (4.54 g, 34.1 mmol) and stir. After 5 minutes, slowly add 1N HCl (200 mL) and heat the reaction to 85° C. for 2 hours forming an orange-red colored solution. Increase the temperature to 100° C. for 10 minutes and cool to room temperature. Pour the reaction mixture over ice and stir for 10 minutes followed by adjustment to pH ˜10 with ammonium hydroxide. Extract the mixture with methylene chloride, pool the organic phases, dry over sodium sulfate, and concentrate in vacuo to give a dark orange-brown oil. Purification on a pre-packed, HMDS treated silica column using a step gradient of 9% to 17% methanol in methylene chloride gives the pure title compound as an orange oil: 1H NMR (400 MHz, dmso-d6): 11.18 (br s, 1H), 7.82 (d, 1H, J=7.6 Hz), 7.40 (d, 1H, J=7.2 Hz), 7.24 (d, 1H, J=2.0 Hz), 7.13 (t, 1H, J=7.6 Hz) 2.76–2.83 (m, 4H). MS (APCI): m/e 229.0 (M+1), 212.0 (M-NH2).

1. customthe reaction to 85° C. for 2 hours
2. customforming an orange-red colored solution
3. temperaturecool to room temperature
4. additionPour the reaction mixture over ice
5. stirringstir for 10 minutes
6. extractionExtract the mixture with methylene chloride, pool the organic phases
7. dry with materialdry over sodium sulfate
8. concentrationconcentrate in vacuo
9. customto give a dark orange-brown oil
10. customPurification on a pre-packed, HMDS
11. additiontreated silica column

ORD record

ord-bce435967368436dbc555201cf4c50a5

Source dataset

uspto-grants-2007_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07157488B2