Trifluoroacetic acid → 5-Ethyl-2-{4-[({6-[4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinyl}pyrimidine

Participants

Reaction Steps

1,1-Dimethylethyl 4-[({6-[4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate (prepared as in Example 73, Step 2, 0.15 g, 0.34 mmol) was dissolved in CH2Cl2 (10 mL). TFA (0.35 mL) was added and the mixture was stirred at ambient temperature for 5 h. An excess of TFA and CH2Cl2 was removed under reduced pressure and the residue was taken up in DMSO (6 mL). Potassium carbonate (1 g) was added, followed by addition of 2-chloro-5-ethylpyrimidine (63 μL, 0.50 mmol). The reaction mixture was degassed, purged with N2 and heated at 100° C. overnight. The mixture was cooled to ambient temperature and poured into water and extracted with EtOAc. The combined organic extract was 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 triturated with hot hexane containing 1% of MeOH to give 0.14 g (92%) of the title compound as a cream-white solid. 1H NMR (400 MHz, CDCl3): δ 8.40 (d, 1H, J=2.7 Hz), 8.19 (bs, 2H), 8.13 (d, 2H, J=8.6 Hz), 8.00 (d, 2H, J=8.6 Hz), 7.73 (d, 1H, J=8.5 Hz), 7.35-7.25 (m, 1H), 4.90-4.75 (m, 2H), 3.94 (d, 2H, J=6.1 Hz), 3.08 (s, 3H), 3.00-2.90 (m, 2H), 2.55-2.40 (m, 2H), 2.25-2.10 (m, 1H), 2.00-1.90 (m, 2H), 1.50-1.30 (m, 2H), 1.19 (t, 3H, J=7.5 Hz); LRMS (APCI), m/z 453 (M+H).

Provenance & Evidence