Sodium Carbonate → 2-Methyl-5-(5-{3,3,3-trifluoro-2-[3-(3-trifluoromethyl-phenyl)-piperidin-1-ylmethyl]-propyl}-[1,3,4]oxadiazol-2-yl)-pyridine

Participants

Reaction Conditions

Reaction Steps

To a round-bottomed flask (5 ml) was added 4,4,4-trifluoro-3-((3-(3-(trifluoromethyl)phenyl)-piperidin-1-yl)methyl)butanoic acid (60 mg, 157 μmol), 6-methylnicotinohydrazide (23.7 mg, 157 μmol) and POCl3 (1.64 g, 1 mL, 10.7 mmol). The reaction mixture was heated to reflux at 110° C. for 4 hr. The crude reaction mixture was allowed to cool to room temperature, poured into ice/water and made basic with a saturated solution of Na2CO3. The reaction mixture was extracted with ethyl acetate, washed with brine and H2O, dried over MgSO4, filtered and concentrated. The resultant residue was purified on a silica column (100% hexane to 60% ethyl acetate/hexane gradient) to afford 12 mg (15%) of 2-methyl-5-(5-{3,3,3-trifluoro-2-[3-(3-trifluoromethyl-phenyl)-piperidin-1-ylmethyl]-propyl}-[1,3,4]oxadiazol-2-yl)-pyridine as an off-white solid. MH+=499.

Provenance & Evidence