Synthesis
Step 2: Synthesis of 6-(2,2,2-trifluoroethoxy)-3-pyridinamine
5-Nitro-2-(2,2,2-trifluoroethoxy)pyridine (20.5 g, obtained from Example 108 Step 1) was dissolved in methanol (160 mL). Palladium/activated carbon catalyst (1.96 g, 10% Pd) was added to the solution and hydrogen was passed through at room temperature. The reaction mixture was stirred under hydrogen atmosphere for 72 hours. Upon completion of the reaction, the reaction mixture was filtered using Dicalite Speed Plus (Acros Organics) and the filter cake was washed with ethyl acetate. The filtrate was concentrated under reduced pressure to remove the solvent. The resulting residue was purified by fast column chromatography (silica gel as stationary phase, heptane/ethyl acetate gradient elution) to afford 6-(2,2,2-trifluoroethoxy)-3-pyridinamine as a brown liquid (16.49 g, 91% yield). Mass spectrometry (MS) data: m/e 193.1 [MH+].
References
[1] Patent: WO2011/45292, 2011, A1. Location in patent: Page/Page column 176
[2] Patent: US2011/92512, 2011, A1. Location in patent: Page/Page column 55
[3] Patent: US2004/63738, 2004, A1
[4] Patent: JP2015/86180, 2015, A. Location in patent: Paragraph 0040
