[OH:1][C:2]1([C:6]2[CH:11]=[C:10]([C:12]([F:15])([F:14])[F:13])[N:9]=[C:8]([O:16][CH:17]3[CH2:22][CH2:21][N:20](C(OC(C)(C)C)=O)[CH2:19][CH2:18]3)[CH:7]=2)[CH2:5][O:4][CH2:3]1.C(=O)(O)[O-].[Na+]>O1CCOCC1.O.OS(O)(=O)=O>[NH:20]1[CH2:19][CH2:18][CH:17]([O:16][C:8]2[CH:7]=[C:6]([C:2]3([OH:1])[CH2:5][O:4][CH2:3]3)[CH:11]=[C:10]([C:12]([F:13])([F:15])[F:14])[N:9]=2)[CH2:22][CH2:21]1A solution of tert-butyl 4-{[4-(3-hydroxyoxetan-3-yl)-6-(trifluoromethyl)pyridin-2-yl]oxy}piperidine-1-carboxylate (0.080 g, 0.17 mmol, from Step 2) in 1,4-dioxane (1.0 mL) was treated with a few drops of water and six drops of concentrated H2SO4 and was stirred overnight. The mixture was made basic with 10 mL of saturated sodium bicarbonate solution and the product was extracted with three portions of DCM. The combined extracts were dried over sodium sulfate, filtered and concentrated to afford crude product, which was used directly in the next step (44 mg, 81%). 1H NMR (300 MHz, CDCl3) δ 7.58 (d, J=1.2 Hz, 1H), 7.18 (s, 1H), 5.22 (tt, J=8.2, 3.9 Hz, 1H), 4.91 (d, J=7.4 Hz, 2H), 4.78 (d, J=7.4 Hz, 2H), 3.10 (dt, J=11.9, 4.3 Hz, 2H), 2.79 (ddd, J=12.5, 9.1, 3.1 Hz, 2H), 2.16-1.98 (m, 2H), 1.70 (dtd, J=12.7, 8.8, 3.8 Hz, 2H). 19F NMR (282 MHz, CDCl3) δ −68.76 (s). LCMS (M+H)+: 319.1.
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