反应详情

温度

110 °C

2,2-Diethylmorpholine hydrochloride (9.6 g) [prepared from the known 2,2-diethyloxirane (B. Rickborn et al, J. Am. Chem. Soc., 1971, 93, 1693) in a similar manner as for the preparation of 2,2-dimethylmorpholine of Example 1] was added to a stirred mixture (3.5:1) of (2α,3α,5α)-2,3-epoxypregnane-11,20-dione 20-cyclic 1,2-ethanediyl acetal and its 3α,4α-epoxy isomer (5.0 g) (prepared as described in British patent 1,039,441) in 1,2-ethanediol (50 ml). Powdered sodium hydroxide (2.14 g) was then added and the mixture was heated at 110° C. for 22 h and then poured into water (500 ml). The precipitated solid was filtered off, washed with water and suspended in a mixture of methanol (45 ml) and water (10 ml). Methanesulfonic acid (1.4 ml) was added and the resulting solution was stirred at room temperature for 45 min and then poured into water (500 ml). After extraction with ethyl acetate, aqueous sodium hydroxide (4M) was added to the aqueous phase until the pH exceeded 9. The precipitated solid was filtered off, washed with water and dissolved in dichloromethane. After washing the solution with water and drying over sodium sulfate, the solvent was removed under reduced pressure to afford an amorphous solid which was crystallised from diethyl ether to give (2β,3α,5α)-2-(2,2-diethyl-4-morpholinyl)-3-hydroxypregnane-11,20-dione (2.04 g). m.p. 177°-179° C.; [α]D +126.0° (c 0.7).

1. filtrationThe precipitated solid was filtered off
2. washwashed with water
3. additionsuspended in a mixture of methanol (45 ml) and water (10 ml)
4. additionMethanesulfonic acid (1.4 ml) was added
5. additionpoured into water (500 ml)
6. extractionAfter extraction with ethyl acetate, aqueous sodium hydroxide (4M)
7. additionwas added to the aqueous phase until the pH
8. filtrationThe precipitated solid was filtered off
9. washwashed with water
10. dissolutiondissolved in dichloromethane
11. washAfter washing the solution with water
12. dry with materialdrying over sodium sulfate
13. customthe solvent was removed under reduced pressure
14. customto afford an amorphous solid which
15. customwas crystallised from diethyl ether