(Diethylamino)sulfur trifluoride → 1-Methylethyl 4-[({2-(fluoromethyl)-6-[4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate

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Reaction Steps

A solution of 1-methylethyl 4-[({2-(hydroxymethyl)-6-[4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate (131 mg, 0.28 mmol) in CH2Cl2 (5 mL) was cooled to −78° C. DAST (0.12 mL, 0.85 mmol) was added dropwise. The reaction mixture was allowed to warm to ambient temperature and stirred overnight. The mixture was poured into aqueous NaHCO3 and extracted with EtOAc (50 mL×2). The combined organic extract was washed with brine and dried over Na2SO4, filtered, and the filtrate was concentrated to a purplish-red oil. The crude material was purified by flash chromatography on a silica gel column eluted with 20% EtOAc/CH2Cl2 to give 86 mg (66%) of the title compound as a white solid. 1H NMR (400 MHz, CDCl3): δ 8.16 (d, 2H, J=8.6 Hz), 8.00 (d, 2H, J=8.3 Hz), 7.80-7.75 (m, 1H), 7.31 (d, 1H, J=8.8 Hz), 5.58 (d, 2H, J=47.4 Hz), 4.92 (septet, 1H, J=6.2 Hz), 4.22 (bs, 2H), 3.92 (d, 2H, J=6.1 Hz), 3.07 (s, 3H), 2.85-2.70 (m, 2H), 2.15-2.00 (m, 1H), 1.90-1.80 (m, 2H), 1.40-1.20 (m, 8H); LRMS (ESI), m/z 465 (M+H).

Provenance & Evidence