Tetrahydrofuran → HCID 22849349, compound

Refer to FIG. 192. Anh. ammonia (ca. 75 ml) was distilled through a KOH tower into a 250 ml flamedried 3-neck flask fitted with an inlet adapter, a magnetic stirring bar, a dry ice/acetone condenser, 35 and a stoDPer. A solution of 6β,19-epoxy-17-iodoandrosta-4,16-diene 3-ethylene ketal (18, 880.4 mg, 1.938 mmol) in dry tetrahydrofuran (THF, 45 ml) was added, followed by metallic sodium (0.20 g, 8.7 mg-atom) cut in small pieces. After stirring under argon pressure for 30 min. the reaction was quenched with the addition of abs. ethanol (1.0 ml). Ammonia was allowed to boil off overnight, 50 ml of water were added, and the mixture was extracted with three 25 ml portions of methylene chloride. The combined organic extracts were washed with 50 ml of brine, dried over magnesium sulfate, and filtered through diatomaceous earth. After washing the residue with 10 ml of methylene chloride the combined filtrates were concentrated under reduced pressure. The intermediate ketal proved remarkably unreactive, but was finally hydrolyzed by refluxing 18 h in 5 ml of chloroform and 2.5 ml of 4 N hydrochloric acid. To the cooled hydrolysis mixture ethyl acetate (50 ml) was added and the layers were separated. The organic phase was washed with 25 ml of saturated sodium bicarbonate+25 ml of brine, dried over magnesium sulfate, and filtered through diatomaceous earth. The residue was washed with 10 ml of ethyl acetate and the combined filtrates were concentrated under reduced pressure. The resulting brown foam was purified by flash chromatography (50% ethyl acetate/hexanes on silica gel) followed by preparative TLC (50% ethyl acetate/hexanes on silica gel GF, 1000μ thickness) to give a partially crystalline film (66.7 mg, 0.233 mmol, 12%). 1H-NMR: 5.92 ∂, 1H, s, 4-H; 5.87-5.64 ∂, 2H, mult., 16,17-H's; 4.10∂ and 3.94 ∂, 2H, AB, 19-H's; 0.79 ∂, 3H, s, 18-Me.

1. distillationAnh. ammonia (ca. 75 ml) was distilled through a KOH tower into a 250 ml
2. customfitted with an inlet adapter, a magnetic stirring bar, a dry ice/acetone condenser
3. customwas quenched with the addition of abs
4. waitto boil off overnight
5. addition50 ml of water were added
6. extractionthe mixture was extracted with three 25 ml portions of methylene chloride
7. washThe combined organic extracts were washed with 50 ml of brine
8. dry with materialdried over magnesium sulfate
9. filtrationfiltered through diatomaceous earth
10. washAfter washing the residue with 10 ml of methylene chloride the combined filtrates
11. concentrationwere concentrated under reduced pressure
12. temperatureby refluxing 18 h in 5 ml of chloroform
13. customTo the cooled hydrolysis mixture ethyl acetate (50 ml)
14. additionwas added
15. customthe layers were separated
16. washThe organic phase was washed with 25 ml of saturated sodium bicarbonate+25 ml of brine
17. dry with materialdried over magnesium sulfate
18. filtrationfiltered through diatomaceous earth
19. washThe residue was washed with 10 ml of ethyl acetate
20. concentrationthe combined filtrates were concentrated under reduced pressure
21. customThe resulting brown foam was purified by flash chromatography (50% ethyl acetate/hexanes on silica gel)
22. customto give a partially crystalline film (66.7 mg, 0.233 mmol, 12%)

ORD record

ord-b262bc51dd1447f5b9eeaff01cc1bedd

Source dataset

uspto-grants-2001_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06331534B1