反应详情

温度

90 °C

A mechanically stirred suspension of 4-(methylbenzyl)hydrazine dihydrochloride (Step 3, 81.8 g, 391 mmol) and methyl acetopyruvate (51.2 g, 356 mmol) in acetic acid (825 mL) was warmed to 90° C. and stirred for 4 h. The solid gradually dissolved, leaving an orange solution. After being cooled to rt, the reaction mixture was concentrated to an orange oil. The organic residue was diluted with EtOAc, washed with water (1×250 mL), NaHCO3 (1×250 mL), and brine (1×250 mL), was dried (Na2SO4), filtered and concentrated to an orange oil. Purification with an ISCO CombiFlash Companion, using a gradient from 0% to 30% EtOAc in hexanes afforded the title compound as a yellow-orange oil (39 g, 45%): 1H NMR (300 MHz, d6-DMSO) δ 2.20 (s, 3H), 2.24 (s, 3H), 3.75 (s, 3H), 5.31 (s, 2H), 6.56 (s, 1H), 7.01 (d, 2H), 7.12 (d, 2H). ES-MS m/z 245.0 (MH)+, HPLC RT (Method A) 3.13 min.

1. dissolutionThe solid gradually dissolved
2. customleaving an orange solution
3. temperatureAfter being cooled to rt
4. concentrationthe reaction mixture was concentrated to an orange oil
5. additionThe organic residue was diluted with EtOAc
6. washwashed with water (1×250 mL), NaHCO3 (1×250 mL), and brine (1×250 mL)
7. dry with materialwas dried (Na2SO4)
8. filtrationfiltered
9. concentrationconcentrated to an orange oil
10. customPurification with an ISCO CombiFlash Companion