1-(1H-Indazol-5-YL)propan-1-one → 4-(1-(4-(2-chloroethoxy)phenyl)-2-(1H-indazol-5-yl)but-1-enyl)-phenol

Participants

Reaction Steps

To a stirred mixture of Zn power (1.65 g, 10.0 eq) in dry THF at rt under N2 was slowly added TiCl4 (4.0 eq, 1.1 mL). The resulting mixture was heated at reflux for 1 h and cooled to rt. A mixture of 1-(1H-indazol-5-yl)propan-1-one (1.3 g, 3.0 eq) and (4-(2-chloroethoxy)phenyl)(4-hydroxyphenyl)methanone (0.7 g, 1.0 eq) in dry THF was added, warmed to 80° C., refluxed for additional 1 h, quenched with Na2CO3 (aq), and extracted with EtOAc. The extract was dried, concentrated, and purified by column chromatography to give the title product (0.3 g, 70%, Z/E=1/1). 1H NMR (400 MHz, CDCl3) δ 7.96 (s, 1H), 7.53 (s, 1H), 7.18 (d, J=8.8 Hz, 2H), 7.12 (d, J=8.4 Hz, 2H), 6.90 (d, J=8.8 Hz, 2H), 6.71-6.88 (m, 1H), 6.72 (d, J=8.8 Hz, 2H), 6.43 (d, J=8.8 Hz, 1H), 4.35 (t, J=7.2 Hz, 1H), 4.24 (t, J=7.2 Hz, 1H), 3.83 (t, J=6.0 Hz, 1H), 3.70 (t, J=6.0 Hz, 1H), 2.47-2.54 (m, 2H), 0.93 (t, J=7.2 Hz, 3H).

Provenance & Evidence