Trifluoroacetic acid → 1-Methylethyl 4-[({6-[2-fluoro-4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate

Participants

Reaction Steps

1,1-Dimethylethyl 4-[({6-[2-fluoro-4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate (prepared as in Example 76, 47 mg, 0.10 mmol) was dissolved in CH2Cl2 (3 mL) and treated with TFA (0.20 mL). The mixture was stirred at ambient temperature for 6 h. The mixture was then cooled to 0° C. in an ice bath, and diisopropylethylamine (1.0 mL) was added, followed by addition of isopropyl chloroformate (1.0M in toluene, 0.12 mL, 0.12 mmol). The reaction mixture was allowed to warm to ambient temperature, and stirred overnight, then diluted with EtOAc, washed with water and brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give the crude product as a light brown solid. The crude product was purified by chromatography on a silica gel column eluted with 25% EtOAc/CH2Cl2 to give 32 mg (70%) of the title compound as a white solid. 1H NMR (400 MHz, CD3OD): δ 8.40 (d, 1H, J=2.9 Hz), 8.20-8.10 (m, 1H), 7.90-7.75 (m, 3H), 7.50 (dd, 1H, Ja=8.8 Hz, Jb=3.0 Hz), 4.90-4.80 (m, 1H), 4.25-4.15 (m, 2H), 4.00 (d, 2H, J=6.1 Hz), 3.18 (s, 3H), 2.95-2.80 (m, 2H), 2.15-2.00 (m, 1H), 1.95-1.85 (m, 2H), 1.40-1.20 (m, 8H); LRMS (ESI), m/z 451 (M+H).

Provenance & Evidence