1,2-Dimethoxyethane → (Z)-2-(6-fluoro-2-hydroxy-1-indanylidene)acetamide

Participants

Reaction Steps

A mixture of (Z)-2-(2-bromo-6-fluoro-1-indanylidene)acetamide (5.30 g, 19.25 mmoles) and silver nitrate (10.40 g, 61.18 mmoles, Aldrich) in dimethoxyethane (265 mL) and water (100 mL) was refluxed for 18 hours. The mixture was filtered, and the filtrate was diluted with water (700 mL) and extracted with ethyl acetate (6×100 mL). The combined extracts were washed with water (200 mL) and brine (200 mL), dried over magnesium sulfate, filtered, and evaporated in vacuo. The residue was chromatographed on silica gel, eluting with hexane:ethyl acetate (2:1), gradually increasing the polarity to hexane:ethyl acetate (1:1). The fractions containing the compound with Rf=0.18 were combined and evaporated in vacuo to give 1.13 g (28%) of crude (Z)-2-(6-fluoro-2-hydroxy-1-indanylidene)acetamide as an orange solid. Recrystallization from ethyl acetate:hexane mixtures gave 0.49 g (12%) of (Z)-2-(6-fluoro-2-hydroxy-1-indanylidene)acetamide as an off-white solid, mp 201°-202° C.; 1H-NMR (DMSO-d6): d 7.73 (d, 2H), 7.19-7.39 (m, 3H), 6.53 (m, 1H), 6.47 (m, 1H), 5.23 (m, 1H), 3.33 (dd, 1H, J=9.6 Hz, 17.0 Hz), and 2.81 (dd, 1H, J=1.6 Hz, 16.3 Hz); steady-state nOe: irradiation at 6.47 d, observed 20% nOe at 7.38 d.

Provenance & Evidence