反应详情

To a stirring solution of 2.0 g (10.30 mmol) of 4,5,6,7-Tetrahydro-1H-indazole-3-carboxylic acid ethyl ester (Ainsworth, C. J. Am. Chem. Soc. 1957, 79, 5242) in 50 mL of DMF is added 1.85 g (13.838 mmol, 1.3 equiv) of K2CO3, followed by 1.35 mL (11.33 mmol, 1.1 equiv) of benzyl bromide. The reaction mixture is stirred 15 min at RT then heated at 60° C. for 16 h. The reaction is cooled to RT, poured into 100 mL 1N HCl, and extracted with Et2O (2×100 mL). The organic layers were washed with H2O (2×100 mL), dried (MgSO4), and the solvent removed in vacuo. Purification of the crude material by silica gel flash column chromatography using a gradient elution of hexane/EtOAc 6/1 to 3/1 afforded 1.05 g of 4,5,6,7-Tetrahydro-1-Benzyl-1H-indazole-3-carboxylic acid ethyl ester as a yellow oil which later solidified: 1H NMR (CDCl3, 300 MHz) δ7.37-7.23 (m, 3H), 7.13 (m, 2H), 5.31 (s, 2H), 4.39 (q, 2H, J=7.2), 2.74 (m, 2H), 2.40 (m, 2H), 1.72 (m, 4H), 1.39 (t, 3H, J=7.2).

1. temperaturethen heated at 60° C. for 16 h
2. temperatureThe reaction is cooled to RT
3. extractionextracted with Et2O (2×100 mL)
4. washThe organic layers were washed with H2O (2×100 mL)
5. dry with materialdried (MgSO4)
6. customthe solvent removed in vacuo
7. customPurification of the crude material by silica gel flash column chromatography
8. washa gradient elution of hexane/EtOAc 6/1 to 3/1