反应详情

温度

-50 °C

A mixture of ferric chloride (anhydrous, 1.63 g, 10.06 mmol) in tetrahydrofuran (anhydrous, 35 ml) is cooled to −50° C. under nitrogen. Methyllithium (3M, 3.4 mL, 10.2 mmol) in diethoxymethane is added to the ferric chloride mixture, maintaining the temperature below −40° C. After this addition is complete methyl magnesium chloride solution (3M, 10.1 ml, 30.18 mmol) in tetrahydrofuran is added maintaining the internal temperature below −40° C. After 10 min. at −40° C., 5α-pregnane-3,20-dione (2.84 g, 9 mmol) is added in one portion with stirring. The temperature is brought to −20° C. and stirred for 3.5 hours. The reaction is quenched by addition of 3 ml of acetic acid and the tetrahydrofuran was removed in vacuo. The residue is partitioned between 100 ml of 3N HCl and 200 ml of ethyl acetate. The organic layer is washed with 1N sodium hydroxide and brine and the solvent is removed in vacuo to afford crude ganaxolone (94.8% purity by HPLC) (Table 1, entry 5)

1. temperaturemaintaining the temperature below −40° C
2. additionAfter this addition
3. additionis added
4. temperaturemaintaining the internal temperature below −40° C
5. customis brought to −20° C.
6. stirringstirred for 3.5 hours
7. customThe reaction is quenched by addition of 3 ml of acetic acid
8. customthe tetrahydrofuran was removed in vacuo
9. customThe residue is partitioned between 100 ml of 3N HCl and 200 ml of ethyl acetate
10. washThe organic layer is washed with 1N sodium hydroxide and brine
11. customthe solvent is removed in vacuo