Dimethyl Sulfoxide → 1,1-dimethylethyl (2S)-2-(1-methylethyl)-4-[3-(methyloxy)-4-nitrophenyl]-1-piperazinecarboxylate

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Reaction Steps

4-Fluoro-2-(methyloxy)-1-nitrobenzene (Example 22, step A) (0.429 g, 2.51 mmol), and K2CO3 (0.410 g, 2.97 mmol) were placed in a flask with 14 mL of DMSO and stirred with a stir bar. 1,1-Dimethylethyl (2S)-2-(1-methylethyl)-1-piperazinecarboxylate (0.521 g, 2.28 mmol) was dissolved in 6.6 mL of THF and added via syringe. The mixture was stirred for 8 days and poured into H2O and EtOAc. The layers were separated, and the organic layer was washed with brine. The combined aqueous layers were extracted with EtOAc. The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. Purification by flash chromatography afforded the title compound of step D (0.515 g, 1.36 mmol, 60%). 1H NMR (400 MHz, DMSO-d6) δ 7.84 (d, J=9.3 Hz, 1H), 6.54 (dd, J=9.4, 2.3 Hz, 1H), 6.43 (d, J=2.4 Hz, 1H), 4.01 (d, J=13.5 Hz, 1H), 3.86 (s, 5H), 3.60-3.75 (m, 1H), 3.22-3.28 (m, 1H), 3.06 (dd, J=13.6, 3.7 Hz, 1H), 2.90-3.02 (m, 1H), 1.79-1.92 (m, 1H), 1.37 (s, 9H), 0.92 (d, J=6.6 Hz, 3H), 0.75 (d, J=6.8 Hz, 3H).

Provenance & Evidence