Benzyl Chloride → 3-Benzyloxy-4-fluoro-phenylamine

Participants

Reaction Steps

79 g (0.62 mol) of 4-fluoro-3-hydroxy-aniline in DMF (1.3 l) were treated under argon portion wise over a period of 15 minutes with 76.7 g (0.68 mol) of potassium t-butylate whereas the temperature of the reaction solution was kept between RT and 28° C. Stirring was continued for 15 minutes then 79 ml (0.68 mol) of benzyl chloride were added dropwise while keeping the temperature of the reaction solution between RT and 30° C. After stirring for 2 h at RT the reaction solution was poured into ice water (6 l) which was then extracted 3-fold with ether (about 3 l each). The combined organic layers were washed with brine (1.5 l) and dried over magnesium sulfate and the solvent removed in vacuo. The residue was purified by chromatography over a short silica gel column with methylene chloride as eluent. Combination of the purified fractions and concentration in vacuo gave 92.7 g (68.6%) of the desired 3-benzyloxy-4-fluoro-phenylamine as light yellow crystalline solid. ISP mass spectrum, m/e: 218.2 (M+1 calculated for C13H12FNO: 218.2).

Provenance & Evidence