反应详情

温度

140 °C

To a solution of (2-isopropyl-phenyl)-hydrazine 7.60 g, 0.0506 mol) (Asselin et al., J. Med. Chem. 1976, 19, 787-792) and acetone (100 mL) is added 1M HCl in EtOH (2 drops). The solution is heated at a reflux overnight. The solution is concentrated, dissolved in toluene (100 mL) and concentrated. The residue is dissolved in o-xylene (100 mL) and ZnCl2 (8.3 g) is added. The solution is heated at 140° C. for 2 hours, cooled to ambient temperature, diluted with EtOAc (200 mL), washed with sat. NH4Cl, dried over Na2SO4, filtered and concentrated. The residue is purified by ISCO (5%-15% EtOAc gradient to furnish the title compound (1.76 g, 10.16 mmol, 20%). 1H NMR (CDCl3), δ 1.43 (d, J=7.0 Hz, 6H), 2.50 (s, 3H), 3.17-3.29 (m, 1H), 6.24-6.27 (m, 1H), 7.02 (d, J=7.1 Hz, 1H), 7.07 (dd, J=7.5, 7.1 Hz, 1H), 7.39 (d, J=7.5 Hz, 1H), 7.85 (bs, 1H) ppm. LC/MS (m/z): calcd. for C12H15N (M+H)+: 174.1. found: 174.1.

1. temperatureThe solution is heated at a reflux overnight
2. concentrationThe solution is concentrated
3. dissolutiondissolved in toluene (100 mL)
4. concentrationconcentrated
5. dissolutionThe residue is dissolved in o-xylene (100 mL)
6. additionZnCl2 (8.3 g) is added
7. temperaturecooled to ambient temperature
8. additiondiluted with EtOAc (200 mL)
9. washwashed with sat. NH4Cl
10. dry with materialdried over Na2SO4
11. filtrationfiltered
12. concentrationconcentrated
13. customThe residue is purified by ISCO (5%-15% EtOAc gradient