反应详情

温度

110 °C

To a round-bottomed flask (5 ml) was added 4,4,4-trifluoro-3-((3-(3-(trifluoromethyl)phenyl)-piperidin-1-yl)methyl)butanoic acid (50 mg, 130 μmol), 4-chlorobenzohydrazide (22.3 mg, 130 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% CH2Cl2 to 40% ethyl acetate/CH2Cl2 eluent) to give an oil. The oil was dissolved in ether/hexane, treated with 4N HCl in dioxane (0.2 ml) and concentrated to afford 40 mg (56%) of 1-{2-[5-(4-chloro-phenyl)-[1,3,4]oxadiazol-2-ylmethyl]-3,3,3-trifluoro-propyl}-3-(3-trifluoromethyl-phenyl)-piperidine hydrochloride as a white solid. MH+=518.

1. temperatureThe reaction mixture was heated
2. customThe crude reaction mixture
3. temperatureto cool to room temperature
4. extractionThe reaction mixture was extracted with ethyl acetate
5. washwashed with brine and H2O
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated
9. customThe resultant residue was purified on a silica column (100% CH2Cl2 to 40% ethyl acetate/CH2Cl2 eluent)
10. customto give an oil
11. concentrationconcentrated