Water → HCID 70048397, compound

Temperature

0 °C

tert-Butyldimethylsilylchloride (9.72 g) was added, at room temperature, to a solution of prasterone (V, 15 g) in pyridine (60 mL). After 24 hrs, the reaction mixture was poured into iced water (600 mL). Ethyl acetate was added, the two layers were separated, the organic layer washed with sodium bicarbonate (5%), sodium dihydrogenphosphate (5%) and brine, dried over sodium sulfate and evaporated to dryness under reduced pressure. The crude residue, [3β-tert-butyldimethylsilyloxy-androst-5-en-17-one, g 23.9; 1H-NMR (300 MHz. CDCl3, ppm from TMS): 5.32 (1H, d), 3.48 (1H, hept), 2.49 (1H, dd), 2.35-0.8 (33H, m), 0.03 (6H, s)] was dissolved in diethyl ether/ethanol (335 mL/250 mL), cooled to 0° C. and treated with sodium borohydride (4 g). The reaction mixture was stirred at room temperature for 1 hr. then quenched with 1N hydrochloric acid to pH=7, diluted with brine (300 mL) and extracted with diethyl ether. The organic layer was separated, dried over sodium sulfate and evaporated to dryness under reduced pressure. The crude residue, [3β-tert-butyldimethylsilyloxy-androst-5-en-17β-ol, g 21; 1H-NMR (300 MHz, CDCl3, ppm from TMS): 5.32 (1H, m), 3.62 (1H, m), 3.48 (1H, hept), 2.35-0.8 (34H, m), 0.03 (6H, s)] was dissolved in tetrahydrofurane (850 mL), cooled to 0° C. and treated with borane-dimethylsulfide complex (THF, 1M, 155 mL). The reaction mixture was stirred at room temperature for 2 hrs, then it was cooled to 0° C. and quenched with water (300 mL), and sodium perborate tetrahydrate (43 g). The mixture was stirred overnight at room temperature, ammonium chloride (30%, 300 mL) was added, the two layers were separated, the organic one dried over sodium sulfate and evaporated under reduced pressure. The crude residue was purified by flash-chromatography (SiO2 ; n-hexane/ethyl acetate 75/25) to give to give 18 g of the title compound (II-a) as a foam. 1H-NMR (300 MHz, CDCl3, ppm from TMS): 3.68 (1H, t), 3.52 (1H, hept), 3.42 (1H, dd), 2.20-0.6 (35H, m), 0.03 (6H, s).

1. customthe two layers were separated
2. washthe organic layer washed with sodium bicarbonate (5%), sodium dihydrogenphosphate (5%) and brine
3. dry with materialdried over sodium sulfate
4. customevaporated to dryness under reduced pressure
5. dissolutionThe crude residue, [3β-tert-butyldimethylsilyloxy-androst-5-en-17-one, g 23.9; 1H-NMR (300 MHz. CDCl3, ppm from TMS): 5.32 (1H, d), 3.48 (1H, hept), 2.49 (1H, dd), 2.35-0.8 (33H, m), 0.03 (6H, s)] was dissolved in diethyl ether/ethanol (335 mL/250 mL)
6. additiontreated with sodium borohydride (4 g)
7. customthen quenched with 1N hydrochloric acid to pH=7
8. additiondiluted with brine (300 mL)
9. extractionextracted with diethyl ether
10. customThe organic layer was separated
11. dry with materialdried over sodium sulfate
12. customevaporated to dryness under reduced pressure
13. dissolutionThe crude residue, [3β-tert-butyldimethylsilyloxy-androst-5-en-17β-ol, g 21; 1H-NMR (300 MHz, CDCl3, ppm from TMS): 5.32 (1H, m), 3.62 (1H, m), 3.48 (1H, hept), 2.35-0.8 (34H, m), 0.03 (6H, s)] was dissolved in tetrahydrofurane (850 mL)
14. temperaturecooled to 0° C.
15. additiontreated with borane-dimethylsulfide complex (THF, 1M, 155 mL)
16. stirringThe reaction mixture was stirred at room temperature for 2 hrs
17. temperatureit was cooled to 0° C.
18. customquenched with water (300 mL), and sodium perborate tetrahydrate (43 g)
19. stirringThe mixture was stirred overnight at room temperature
20. additionammonium chloride (30%, 300 mL) was added
21. customthe two layers were separated
22. dry with materialthe organic one dried over sodium sulfate
23. customevaporated under reduced pressure
24. customThe crude residue was purified by flash-chromatography (SiO2 ; n-hexane/ethyl acetate 75/25)
25. customto give

ORD record

ord-26f9770086524b818f6e9f7c3bc169cf

Source dataset

uspto-grants-1999_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05914324