4-Fluoro-3-methylbenzaldehyde → 8-(4-Fluoro-3-methylphenyl)oct-7-enoic acid

To a suspension of 7-Carboxyheptanyltriphenylphosphonium bromide (9.240 g, 19.602 mmol) in 100 mL of benzene, was added t-BuOK (58.8 mL, 58.8 mmol, 1M in THF). The resulting mixture was refluxed for 1 h and then 4-fluoro-3-methylbenzaldehyde (1.43 mL, 11.761 mmol) was added via a syringe. The mixture was refluxed under N2 for an additional 63 h. After cooling to room temperature, the reaction mixture was washed with water (80 mL) and the aqueous layer was acidified with concentrated HCl to pH=2 and extracted with ethyl acetate (30 mL×3). The combined organic extracts dried (Na2SO4), filtered, and concentrated under reduced pressure. The product was isolated by Flash column chromatography (silica gel column) eluting with 0-30% ethyl acetate/hexanes to give the title compound as colorless oil (3.150 g, >99% yield). LC-MS: tR=9.6 min, m/z 251 (M+H)+.

1. temperatureThe resulting mixture was refluxed for 1 h
2. temperatureThe mixture was refluxed under N2 for an additional 63 h
3. washthe reaction mixture was washed with water (80 mL)
4. extractionextracted with ethyl acetate (30 mL×3)
5. dry with materialThe combined organic extracts dried (Na2SO4)
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customThe product was isolated by Flash column chromatography (silica gel column)
9. washeluting with 0-30% ethyl acetate/hexanes

ORD record

ord-7f6e31abf4c648d089b6be43018fad0b

Source dataset

uspto-grants-2012_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08242174B2