反应详情

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).

1. customwas kept between RT and 28° C
2. customthe temperature of the reaction solution between RT and 30° C
3. stirringAfter stirring for 2 h at RT the reaction solution
4. extractionwas then extracted 3-fold with ether (about 3 l each)
5. washThe combined organic layers were washed with brine (1.5 l)
6. dry with materialdried over magnesium sulfate
7. customthe solvent removed in vacuo
8. customThe residue was purified by chromatography over a short silica gel column with methylene chloride as eluent
9. concentrationCombination of the purified fractions and concentration in vacuo