4-Pentafluoroethyloxy-piperidine synthesis

Yield: 11.9%

Reaction Conditions:

with 5% rhodium-on-charcoal;hydrogen;acetic acid in ethanol at 80; under 67506.8 Torr;

Steps:

5.2 Step 2: Synthesis of 4-(2,2,2-trifluoroethoxy) piperidine
[00315] 4-(2,2,2-trifluoroethoxy)pyridine (EV-AQ7197-001, 510 mg, 2.88 mmol) was dissolved in EtOH: acetic acid (3: 1, 60 mL) and subjected to H-cube hydrogenation (lml/min, 90 bar, 80 °C) over a 5% Rh/C cat cart. The reaction mixture was concentrated in vacuo to afford the title compound (104 mg, 11.9%) as a tan gum. [00316] Method B: LC-MS: m/z = 184.0 (M+H)+, RT = 0.21-0.33 min.

References:

QUARTET MEDICINE, INC.;ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE (EPFL);TEBBE, Mark, Joseph;ATTON, Holly, Victoria;AVERY, Craig;BROMIDGE, Steven, Mark;KERRY, Mark;KOTEY, Adrian, Kotei;MONCK, Nathaniel, J.;MENICONI, Mirco;RIDGILL, Mark, Peter;TYE, Heather;SAIAH, Eddine;JOHNSSON, Kai, Peter;GORSKA, Katarzyna, Irena;PENG, Hairuo;MCCALL, John, Michael WO2017/59191, 2017, A1 Location in patent:Paragraph 00313-00316