反应详情

温度

60 °C

The free acid obtained in Step A was dissolved in THF (42 mL) and then water was added (42 mL). Sodium bicarbonate (5.63 g, 66.83 mmol) was added slowly (evolution of gas is observed) to afford a homogeneous solution. Sodium dithionite (10.32 g, 50.41 mmol) was added portion wise as a solid over 60 minutes while stirring vigorously (evolution of gas is observed). HPLC analysis after 15 minutes showed the reaction was complete. The reaction mixture was diluted with saturated sodium chloride solution (42 mL) and ethyl acetate (42 mL) and the layers were separated. The organic layer was treated with 1N methanolic HCl (17 mL) and heated to 60° C. for 5 minutes and cooled slowly to room temperature. The reaction mixture was concentrated on a rotary evaporator and the resultant residue was partitioned between ethyl acetate (100 mL) and water (100 mL). The organic layer was washed with saturated sodium bicarbonate solution (2×100 mL) and concentrated on a rotary evaporator to afford 5.53 g (92%) of crude product as a yellow semi-solid. This material was dissolved in ethanol (24 mL) and heated to reflux and water was slowly added (24 mL). Preferably, a seed crystal of the title compound was added resulting in crystallization of the product while still hot. The material was stirred for 2 hours at room temperature and filtered, washed with 1:3 ethanol/water (50 mL), air and vacuum dried to afford 4.95 g of the title compound (83% yield, 99% by HPLC) as a light yellow crystalline solid which can readily be decolorized with neutral charcoal.

1. customto afford a homogeneous solution
2. customthe layers were separated
3. additionThe organic layer was treated with 1N methanolic HCl (17 mL)
4. temperaturecooled slowly to room temperature
5. concentrationThe reaction mixture was concentrated on a rotary evaporator
6. customthe resultant residue was partitioned between ethyl acetate (100 mL) and water (100 mL)
7. washThe organic layer was washed with saturated sodium bicarbonate solution (2×100 mL)
8. concentrationconcentrated on a rotary evaporator
9. customto afford 5.53 g (92%) of crude product as a yellow semi-solid
10. temperatureheated
11. temperatureto reflux