反应详情

温度

0 °C

To a cooled mixture (internal temp. 2° C.) of 1-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-{[(1S)-2-hydroxy-1-phenylethyl]amino}ethanone (44.9 g) in methanol (450 ml) under nitrogen was added CaCl2.2H2O (38.7 g) in one portion resulting in a slight exotherm (max temp ˜12° C.). After the resulting clear solution had cooled to 0° C., sodium borohydride (10.5 g) was added in four portions over a 50 min period. After a further 2h at this temperature the volatile material was removed in vacuo resulting in a thick white slurry, to which ethyl acetate (500 ml) was added. The mixture was filtered through a short plug of Hyflo Supercel and the filtrate washed with water (150 ml), brine (150 ml), dried (Na2SO4) and concentrated in vacuo to give a thick orange oil. The oil was dissolved in acetonitrile (150 ml) and cooled to 5° C. for 18 h. The resulting crystals were filtered and washed with acetonitrile (3×30 ml) to give the title compound (23.9 g). The mother liquor from the filtration was concentrated in vacuo and taken up in acetonitrile (50 ml), cooled to 5° C. for 18 h to provide (after filtration and washing) a second crop of the title compound (3.4 g).

1. customresulting in a slight exotherm (max temp ˜12° C.)
2. customAfter a further 2h at this temperature the volatile material was removed in vacuo
3. customresulting in a thick white slurry, to which ethyl acetate (500 ml)
4. additionwas added
5. filtrationThe mixture was filtered through a short plug of Hyflo Supercel
6. washthe filtrate washed with water (150 ml), brine (150 ml)
7. dry with materialdried (Na2SO4)
8. concentrationconcentrated in vacuo
9. customto give a thick orange oil
10. temperaturecooled to 5° C. for 18 h
11. filtrationThe resulting crystals were filtered
12. washwashed with acetonitrile (3×30 ml)