1-Butanol → 2-(Dibutoxymethyl)-4-fluoro-1-nitrobenzene

Participants

Reaction Steps

A solution of 5-fluoro-2-nitrobenzaldehyde (1-15, 75 g, 443 mmol), para-toluenesulfonic acid monohydrate (8.4 g, 44.3 mmol), and n-butanol (122 mL, 1.33 mol) was refluxed in toluene (630 mL) using a Dean-Stark apparatus for 15 h. The reaction was cooled, concentrated and partitioned between water (1 L) and EtOAc (1 L). The organic layer was washed with water (1 L) and brine (1 L), dried over Na2SO4 and concentrated. The crude reaction was purified by column chromatography (0 to 25% EtOAc in hexanes, 1% triethylamine buffer) to yield the 2-(dibutoxymethyl)-4-fluoro-1-nitrobenzene (1-16) as an oil. Data for 1-16: 1H NMR (500 MHz, CDCl3) δ 7.92 (dd, J=8.5, 4.5 Hz, 1H), 7.54 (dd, J=9.0, 3.0 Hz, 1H), 7.15-7.11 (m, 1H), 6.05 (s, 1H), 3.67-3.52 (m, 4H), 1.63-1.57 (m, 4H), 1.43-1.35 (m, 4H), 0.94-0.91 (m, 6H) ppm; ESI MS [M+H] for C15H22FNO4 (-acetal)=169.8.

Provenance & Evidence