Diethyl Ether → HCID 67955066, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-{[1-(tert-butoxycarbonyl)piperidin-4-yl]oxy}-6-(trifluoromethyl)isonicotinic acid (1.4 g, 3.6 mmol, prepared by the method of Step 2) in methanol (70. mL) at 0° C. was added 2.0 M trimethylsilyldiazomethane in ether (18 mL, 36 mmol) dropwise until TLC indicated complete reaction. Excess reagent was discharged by dropwise addition of acetic acid to the mixture cooled in an ice bath. Solvent was removed by rotary evaporation. The residue was dissolved in ethanol (28 mL), cooled to 0° C., and sodium tetrahydroborate (0.26 g, 7.0 mmol) was added. The cooling was discontinued and the reaction was allowed to stir at room temperature for 30 minutes. It was re-cooled in an ice bath and an additional portion of Sodium tetrahydroborate (0.27 g, 7.2 mmol) was added. The reaction mixture was allowed to reach room temperature and stir until the reaction was complete as determined by analytical LCMS and TLC. The reaction was quenched by the addition of saturated ammonium chloride, diluted with water, and extracted with EtOAc (2×). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered and concentrated. Flash chromatography, using a 120 g silica gel cartridge and eluting with a gradient from 0-30% EtOAc in hexanes afforded product as a colorless oil (0.90 g, 67%). 1H NMR (400 MHz, CDCl3) δ 7.22 (s, 1H), 6.90 (s, 1H), 5.27 (tt, J=7.7, 3.7 Hz, 1H), 4.74 (d, J=2.5 Hz, 2H), 3.81-3.63 (m, 2H), 3.31 (ddd, J=13.4, 8.4, 3.7 Hz, 2H), 1.98 (ddt, J=13.5, 7.0, 3.8 Hz, 2H), 1.72 (dtd, J=12.5, 8.2, 4.0 Hz, 2H), 1.47 (s, 9H). 19F NMR (376 MHz, CDCl3) δ −69.21 (s). LCMS (M-tBu+H)+: 321.1.

Provenance & Evidence