反应详情

温度

3 °C

In a 5 L one-neck flask four-necked flask (equipped with mechanical stirrer, nitrogen inlet, thermocouple, and glass stopper), was charged the solution of (R)-[1-(2,2-dimethyl-4,6-dioxo-[1,3]dioxane-5-carbonyl)-2-methyl-propyl]-carbamic acid, tert-butyl ester in dichloromethane prepared in Step A above, (˜3.2 L). The reaction was chilled to ˜3° C. in an ice bath, and acetic acid was added (437 g, 7.27 mol). The reaction mixture was then treated with sodium borohydride granules (62.5 g, 1.65 mol), which were added in portions over 1 h. During the addition the reaction temperature increased to ˜9° C. and was stirred at that temperature 1.5 h and then was split into two portions. Each portion was poured into brine (1 L), stirred (magnetically) for 20 minutes, and partitioned. Each organic phase washed with brine (3×750 mL) and distilled water (2×500 mL). The combined organic phases were dried (MgSO4) and concentrated to yield crude product. The crude product was dissolved in heptane-dichloromethane (˜1:1) and loaded onto a Biotage 150M cartridge (2.5 kg silica gel) and then eluted with heptane (2 L), 15:85 (14 L), 3:7 (16 L), and 1:1 ethyl acetate-heptane (8 L) to give two main fractions. The first fraction yielded the desired material contaminated with minor impurities.

1. customIn a 5 L one-neck flask four-necked flask (equipped with mechanical stirrer, nitrogen inlet
2. additionwere added in portions over 1 h
3. additionDuring the addition the reaction temperature
4. temperatureincreased to ˜9° C.
5. customwas split into two portions
6. additionEach portion was poured into brine (1 L)
7. stirringstirred (magnetically) for 20 minutes
8. custompartitioned
9. washEach organic phase washed with brine (3×750 mL)
10. distillationdistilled water (2×500 mL)
11. dry with materialThe combined organic phases were dried (MgSO4)
12. concentrationconcentrated
13. customto yield crude product
14. washeluted with heptane (2 L), 15:85 (14 L), 3:7 (16 L), and 1:1 ethyl acetate-heptane (8 L)
15. customto give two main fractions