反应详情

To a stirred ice-cooled suspension of sodium hydride, (60% dispersion in mineral oil, 0.83 g, 21 mmol) in DMF (15 mL) was added a suspension of tert-butyl 3-oxopiperazine-1-carboxylate (2.5 g, 12 mmol) in DMF (45 mL) through a syringe. The ice-H2O bath was removed and the resulting mixture, which was a suspension, was stirred at ambient temperature for 30 min. Complete dissolution was observed. 2-chloro-5-(chloromethyl)pyridine (2.0 g, 12 mmol) was added in one portion as a solid. The resulting mixture was stirred at ambient temperature for 18 h then poured into ice and saturated NaHCO3 aqueous solution. It was extracted with ethyl acetate (2×). The combined organics were washed with saturated NaHCO3 aqueous solution (3×), dried over Na2SO4, and concentrated in vacuo. The residue was subjected to combi-flash column chromatography (methanol/DCM) to give compound 358 (3.65 g, 91% yield) as a white solid. 1H NMR (500 MHz, CDCl3) δ ppm 8.31 (1 H, d, J=2.2 Hz), 7.65 (1 H, dd, J=8.3, 2.4 Hz), 7.33 (1 H, d, J=8.1 Hz), 4.59 (2 H, s), 4.15 (2 H, s), 3.62 (2 H, t, J=5.4 Hz), 3.29 (2 H, t, J=5.1 Hz), 1.46 (9 H, s). LCMS-ESI (POS), M/Z, M+1: Found 326.0.

1. additionwas added
2. customThe ice-H2O bath was removed
3. dissolutionComplete dissolution
4. stirringThe resulting mixture was stirred at ambient temperature for 18 h
5. extractionIt was extracted with ethyl acetate (2×)
6. washThe combined organics were washed with saturated NaHCO3 aqueous solution (3×)
7. dry with materialdried over Na2SO4
8. concentrationconcentrated in vacuo