反应详情

温度

59 °C

A mixture of 4-bromo-2,6-difluorobenzaldehyde, available from Sigma-Aldrich, (500 mg, 2.26 mmol) and morpholine (0.198 ml, 2.26 mmol) was prepared in chloroform (10 ml) at room temperature and heated to 58-60° C. in a sealed tube for 1 h. The mixture was then cooled to room temperature and sodium triacetoxyborohydride (719 mg, 3.39 mmol) was added and the mixture heated again to 58-60° C. in a sealed tube for 60 h. The mixture was allowed to cool down to room temperature and then washed with water (5 ml), filtered through a phase separator and concentrated in vacuo. Crude 1HNMR (CDCl3) suggested an 8:2 mixture of the desired amine to the imine product. After initial chromatography (1-5% methanol/dichloromethane) which did not separate products, mixture was purified by preparative HPLC to afford 4-(4-bromo-2,6-difluorobenzyl)morpholine as a colourless oil (247 mg, 0.85 mmol, 37%).

1. temperatureThe mixture was then cooled to room temperature
2. temperaturethe mixture heated again to 58-60° C. in a sealed tube for 60 h
3. temperatureto cool down to room temperature
4. washwashed with water (5 ml)
5. filtrationfiltered through a phase separator
6. concentrationconcentrated in vacuo
7. additionan 8:2 mixture of the desired amine to the imine product
8. customAfter initial chromatography (1-5% methanol/dichloromethane) which did not separate products, mixture
9. customwas purified by preparative HPLC