Hydrochloric Acid → 2-[6-(Trifluoromethyl)pyridin-2-yl]propan-2-amine

Participants

Reaction Conditions

Reaction Steps

Add N-[1-methyl-1-(6-trifluoromethyl-pyridin-2-yl)-ethyl]-acetamide (20 g; 81.2 mmol) to a mixture of water (30 mL) and concentrated hydrochloric acid (30 mL; 365 mmol). Heat the mixture to 90° C. for 16 hours. Cool the mixture to 15° C. and add 100 mL 5 N sodium hydroxide to pH 13. Extract the mixture three times with t-butylmethyl ether (100 mL). Combine the t-butylmethyl ether layers and extract with 1 N HCl (100 mL), then twice with 0.5 N HCl (100 mL). Combine the acidic aqueous layers and stir with t-butylmethyl ether (50 mL). Clarify the mixture by filtration and separate the layers. Add brine (100 mL) and 5 N NaOH (70 mL) to pH 13. Extract the aqueous layer 3 times with t-butylmethyl ether (100 mL). Combine the t-butylmethyl ether layers and wash with a mixture of brine (95 mL) and 5 N NaOH (5 mL). Separate the layers and add sodium sulfate to the t-butylmethyl ether layer. Filter and concentrate the filtrate under reduced pressure to afford the title compound as a brown oil (14.2 g, 69.54 mmol; 86%) 1H NMR 500.174 MHz (CDCl3) δ 7.79 (t, J=7.96 Hz, 1H), 7.64 (d, J=7.69 Hz, 1H), 7.49 (d, J=7.69 Hz, 1H), 2.0 (s, 2H), 1.50 (s, 6H). HRMS (ESI) m/z (M+H)1 calcd for C9H12F3N2: 205.0947, found 205.0946.

Provenance & Evidence