1-Bromo-2,3-difluorobenzene → 5-(2,3-Difluorophenyl)nona-1,8-dien-5-ol

Temperature

-78 °C

In an oven-dried 250 mL round-bottomed flask (t=g) was added 1-Bromo-2,3-difluorobenzene (2.304 mL, 20.58 mmol) in THF (60 mL) to give a colorless solution. After cooling to −78° C., BuLi (8.23 mL, 20.58 mmol) was added dropwise via syringe. The mixture was stirred at −78° C. for 20 minutes, and nona-1,8-dien-5-one (2.37 g, 17.15 mmol) (azeotroped with dry benzene) was added dropwise via canuula (plus 6 ml THF rinse). The mixture was warmed up to room temperature over 1 hour. Quenched with water and the THF solvent was stripped off. The remaining mixture was extracted with EtOAc. The layers were separated and the organic layer was washed with brine, dried with Na2SO4, and concentrated to a yellow oil. The residue was purified by FCC up to 35% Et2O/hexane. The desired fractions were pooled and concentrated to the product as a colorless oil (2.39 g, 55.3%). 1H NMR (400 MHz, CDCl3) δ 7.30-7.22 (m, 1H), 7.10-7.03 (m, 2H), 5.82-5.70 (m, 2H), 4.97-4.85 (m, 4H), 2.20-2.00 (m, 4H), 2.00-1.75 (m, 4H).

1. customto give a colorless solution
2. temperatureThe mixture was warmed up to room temperature over 1 hour
3. customQuenched with water
4. extractionThe remaining mixture was extracted with EtOAc
5. customThe layers were separated
6. washthe organic layer was washed with brine
7. dry with materialdried with Na2SO4
8. concentrationconcentrated to a yellow oil
9. customThe residue was purified by FCC up to 35% Et2O/hexane
10. concentrationconcentrated to the product as a colorless oil (2.39 g, 55.3%)

ORD record

ord-1b0774a2e3ba43fe9cf4e39a2cba68a5

Source dataset

uspto-grants-2011_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08044043B2