Diethyl Ether → 5-(2,3-Difluorophenyl)nona-1,8-dien-5-ol

Temperature

-78 °C

In a 500 mL round-bottomed flask (t=g) was added crude 4-iodobut-1-ene (11.51 g, 63.2 mmol) in Et2O (100 mL) to give a colorless solution. After cooling to −78° C. under nitrogen, tBuLi (80 mL, 136 mmol) was added dropwise via syringe. The mixture was slowly warmed up to room temperature while stirring for 2 hours. After 20 minutes at room temperature, the mixture was cooled to −78° C. and ethyl 2,3-difluorobenzoate (4.28 mL, 28.7 mmol) was added dropwise via syringe. The mixture was gradually warmed up to room temperature over 30 minutes. The reaction was quenched by water and the volatiles were evaporated. The residue was partitioned between water and EtOAc. The layers were separated and the organic layer was washed with brine, dried with Na2SO4 and concentrated to a light yellow oil. Purification up to 40% Et2O in hexane afforded the desired product as a colorless oil: (1.41 g, 19%). 1H NMR (400 MHz, CDCl3) δ 7.31-7.22 (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 slowly warmed up to room temperature
3. waitAfter 20 minutes at room temperature
4. temperaturethe mixture was cooled to −78° C.
5. temperatureThe mixture was gradually warmed up to room temperature over 30 minutes
6. customThe reaction was quenched by water
7. customthe volatiles were evaporated
8. customThe residue was partitioned between water and EtOAc
9. customThe layers were separated
10. washthe organic layer was washed with brine
11. dry with materialdried with Na2SO4
12. concentrationconcentrated to a light yellow oil
13. customPurification up to 40% Et2O in hexane

ORD record

ord-4ba70f0bd66e48d398cdfabbfd6f4952

Source dataset

uspto-grants-2011_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08044043B2