反应详情

温度

55 °C

A mixture of Example 93B (2.15 g, 78% potency, 4.24 mmol) in THF (6.5 mL) was treated with a solution of 2M LiBH4 in THF (3.3 mL, 6.1 mmol), heated to 55° C. for 3 hours, cooled to room temperature, treated with 20% citric acid (12 mL), warmed to 50° C. for 30 minutes, and extracted with MTBE (2×20 mL). The aqueous phase was adjusted to pH>10 with 50% NaOH and extracted with 5:1 THF/ethyl acetate (2×30 mL). The combined organic phases were concentrated, treated with citric acid (1.0 g), and concentrated to a volume of approximately 6 mL. The solution was adjusted to pH>10 with 50% NaOH, stirred for 2 hours, and filtered. The filter cake was washed with water (2 mL) and dried under vacuum with an air bleed to provide 670 mg (61% potency, 40% potency adjusted yield) of the desired product as one enantiomer in high excess. MS (ACPI) m/e 244 (M+H)+; 1H NMR (CD3OD) δ 7.70 (d, 2H) 7.55 (s, 1H) 7.54 (d, 2H) 7.18 (s, 1H) 4.00 (d, 1H) 3.89 (d, 1H) 3.30 (s, 3H).

1. temperaturecooled to room temperature
2. temperaturewarmed to 50° C. for 30 minutes
3. extractionextracted with MTBE (2×20 mL)
4. extractionextracted with 5:1 THF/ethyl acetate (2×30 mL)
5. concentrationThe combined organic phases were concentrated
6. additiontreated with citric acid (1.0 g)
7. concentrationconcentrated to a volume of approximately 6 mL
8. filtrationfiltered
9. washThe filter cake was washed with water (2 mL)
10. customdried under vacuum with an air bleed
11. customto provide