Water → 1-{1-[2-Ethyl-5-(ethyloxy)-4-nitrophenyl]-4-piperidinyl}-4-(methylsulfonyl)piperazine

Participants

Reaction Conditions

Reaction Steps

A mixture of 1-ethyl-4-(ethyloxy)-2-fluoro-5-nitrobenzene (Example 208, step A) (0.80 g, 3.75 mmol), 1-(methylsulfonyl)-4-(4-piperidinyl)piperazine (0.928 g, 3.75 mmol) and K2CO3 (0.622 g, 4.50 mmol) in DMSO (20 mL) was heated at 90° C. for 48 h. The reaction had not progressed sufficiently so the reaction was then heated at 120° C. for an additional 4 h. The reaction was cooled to rt, poured into H2O and extracted exhaustively with DCM. The combined organics were washed with H2O then dried over MgSO4. The resultant solution was concentrated onto silica and purified by flash chromatography to afford 1-{1-[2-ethyl-5-(ethyloxy)-4-nitrophenyl]-4-piperidinyl}-4-(methylsulfonyl)piperazine (0.551 g, 33%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.75 (s, 1H), 6.74 (s, 1H), 4.19 (q, J=6.93 Hz, 2H), 3.19-3.28 (m, 2H), 3.06-3.14 (m, 4H), 2.87 (s, 3H), 2.52-2.79 (m, 9H), 1.80-1.92 (m, 2H), 1.46-1.67 (m, 2H), 1.33 (t, J=6.97 Hz, 3H), 1.19 (t, J=7.47 Hz, 3H).

Provenance & Evidence