Hydrochloric Acid → 2-[6-(Trifluoromethyl)pyridin-3-yl]propan-2-amine

Participants

Reaction Conditions

Reaction Steps

Heat a mixture of N-[1-Methyl-1-(6-trifluoromethyl-pyridin-3-yl)-ethyl]-acetamide (93.5 moles, 19.1 kg), concentrated hydrochloric acid (805.9 moles; 66.2 L; 79.4 kg), and water (79.4 L; 79.4 kg) to 95-100° C. with stirring under nitrogen for 24 hours. Cool the reaction mixture to 20-35° C. and observe completion of the reaction by HPLC. Cool the reaction vessel to 10-20° C. and add tert-butyl methyl ether (105.4 L; 78.0 kg). Separate the phases, and discard the organic layer. Add 15% sodium hydroxide (910.9 moles; 205 L; 242.9 kg) to the aqueous phase and observe a pH of 9.5-10.5. Extract the aqueous layer with ethyl acetate (3×89 mL; 3×80.0 kg), combine the organic layers, and discard the aqueous phase. Concentrate the solution to approximately 2 volumes, add tert-butyl methyl ether (174 L; 129.1 kg), and concentrate the solution to approximately 2 volumes. Dilute the reaction vessel with n-heptane (168 L; 115.0 kg), concentrate the solution to approximately 2 volumes, and dilute with additional n-heptane (30 L, 20.7 kg). Cool the contents of the reaction mixture to 0-5° C. and stir the mixture for 2 hours at 0-5° C. Filter and dry the resultant solids under vacuum at 35-45° C. to afford the titled compound (14.19 kg; 74.3%, based on HPLC) as a 97.9% pure tan powder.

Provenance & Evidence