Hydrochloric Acid → (5-Bromo-2-ethylthiophen-3-yl)(cyclohexyl)methanol

To a solution (40 mL) of ethyl 5-bromo-2-ethylthiophene-3-carboxylate (3.69 g) synthesized in Example 69 (4) in tetrahydrofuran was added 1.5M diisobutylaluminum hydride-toluene solution (26.4 mL) at 0° C., and the mixture was stirred for 1 hr. 1N Hydrochloric acid was added to quench the reaction, and the mixture was extracted with ethyl acetate. The extract was washed with 1N hydrochloric acid and brine, dried over magnesium sulfate and concentrated under reduced pressure to give a pale-yellow oil. To a solution of the obtained oil in tetrahydrofuran (30 mL) was added activated manganese dioxide (15.8 g), and the mixture was stirred at room temperature overnight and at 50° C. for 2 hr. Manganese dioxide was filtered off, and the filtrate was concentrated under reduced pressure to give a brown oil. To a solution of the obtained oil in tetrahydrofuran (60 mL) was added dropwise 1.0M cyclohexylmagnesium bromide-tetrahydrofuran solution (39.6 mL) at −78° C., and the mixture was stirred for 1 hr. Saturated aqueous ammonium chloride solution was added to quench the reaction, and the mixture was extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=3:17, volume ratio) to give the title compound (2.53 g, 60%) as a yellow oil.

1. customto quench
2. customthe reaction
3. extractionthe mixture was extracted with ethyl acetate
4. washThe extract was washed with 1N hydrochloric acid and brine
5. dry with materialdried over magnesium sulfate
6. concentrationconcentrated under reduced pressure
7. customto give a pale-yellow oil
8. stirringthe mixture was stirred at room temperature overnight and at 50° C. for 2 hr
9. filtrationManganese dioxide was filtered off
10. concentrationthe filtrate was concentrated under reduced pressure
11. customto give a brown oil
12. stirringthe mixture was stirred for 1 hr
13. customto quench
14. customthe reaction
15. extractionthe mixture was extracted with ethyl acetate
16. washThe extract was washed with brine
17. dry with materialdried over magnesium sulfate
18. concentrationconcentrated under reduced pressure
19. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=3:17, volume ratio)

ORD-Eintrag

ord-9972516afeca4644891fb548d793549e

Quelldatensatz

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08309580B2