反应详情

温度

125 °C

A solution of (R)-(−)-1-amino-propan-2-ol (389 g, 5.19 mol) in dimethyl sulfoxide (600 mL) was added to a solution of the product from Step A (786 g, 3.46 mol), basic alumina (786 g), and 4A molecular sieves (131 g). The stirred mixture was heated at 110-140° C. for 24 h, cooled and filtered, the filter-aide was washed with 10 L of 4:1 ether-ethyl acetate followed by 4 L of 3:2 ethyl acetate-hexane. The organic washes were extracted with water (5 L) and the aqueous phase was extracted with 25% ethyl acetate-hexane (4×2 L). The combined organic phases were washed with water and brine, dried over sodium sulfate, concentrated to about 3 L and allowed to stand for 48 h. The precipitated solid was collected by filtration, washed with hexane, and vacuum-dried to provide the desired product in two crops (619 g and 86 g). The concentated supernatant was applied to a 5 kg silica gel pad and eluted with a gradient of 10-50% ethyl acetate-hexane to give, after concentration in vacuo, additional product (119 g): total yield was 791 g (81%).

1. temperaturecooled
2. filtrationfiltered
3. washthe filter-aide was washed with 10 L of 4:1 ether-ethyl acetate
4. extractionThe organic washes were extracted with water (5 L)
5. extractionthe aqueous phase was extracted with 25% ethyl acetate-hexane (4×2 L)
6. washThe combined organic phases were washed with water and brine
7. dry with materialdried over sodium sulfate
8. concentrationconcentrated to about 3 L
9. filtrationThe precipitated solid was collected by filtration
10. washwashed with hexane
11. customvacuum-dried