Florhydral → 2-Ethoxy-4-(4-(3-isopropylphenyl)pent-1-enyl)phenol

Temperature

65 °C

(4-(tert-Butyldimethylsilyloxy)-3-ethoxyphenyl)methyltriphenylphosphonium bromide (1.15 g, 1.89 mmol, 1.0 equiv.) in THF (8 mL), was cooled to 0° C. After adding n-BuLi (1.6 M in hexanes, 1.2 mL, 1.89 mmol, 1.0 equiv.) at 0° C., the red solution was stirred at 65° C. for 1 h. The mixture was re-cooled to 0° C., 3-(3-isopropylphenyl)butanal (541 mg, 2.84 mmol, 1.5 equiv.) in THF (3 mL) was added, and the mixture was stirred at 65° C. for 18 h. After addition of H2O, the aqueous layer was extracted with cyclohexane (2×), the combined organic phases were washed with brine, dried (MgSO4), filtered and the filtrate was concentrated. The residue was purified by flash chromatography on SiO2 (cyclohexane/EtOAc 98:2) to yield a colorless oil which was dissolved in THF (10 mL). n-Bu4NF (1.0 M in THF, 2.3 mL, 2.27 mmol, 1.2 equiv.) was added, and the mixture was stirred at 25° C. for 1 h. After addition of H2O, the aqueous layer was extracted with EtOAc (2×), the combined organic phases were washed with brine, dried (MgSO4), filtered and the filtrate was concentrated. The residue was purified by flash chromatography on SiO2 (cyclohexane/EtOAc 19:1→9:1) to yield 0.33 g (54% over 2 steps) of the title compound as a yellow oil.

1. temperatureThe mixture was re-cooled to 0° C.
2. stirringthe mixture was stirred at 65° C. for 18 h
3. extractionthe aqueous layer was extracted with cyclohexane (2×)
4. washthe combined organic phases were washed with brine
5. dry with materialdried (MgSO4)
6. filtrationfiltered
7. concentrationthe filtrate was concentrated
8. customThe residue was purified by flash chromatography on SiO2 (cyclohexane/EtOAc 98:2)
9. customto yield a colorless oil which
10. stirringthe mixture was stirred at 25° C. for 1 h
11. extractionthe aqueous layer was extracted with EtOAc (2×)
12. washthe combined organic phases were washed with brine
13. dry with materialdried (MgSO4)
14. filtrationfiltered
15. concentrationthe filtrate was concentrated
16. customThe residue was purified by flash chromatography on SiO2 (cyclohexane/EtOAc 19:1→9:1)

ORD record

ord-7a79a6170ee044f08b29d97c57989b26

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09193935B2