2'-Fluoro-4'-methoxyacetophenone → Benzene, 2-fluoro-4-methoxy-1-(1-methylethenyl)-

Temperature

-78 °C

A solution of sodium bis(trimethylsilyl)-amide, 1.0M in tetrahydrofuran (714 ml, 0.714 m) was added to a suspension of methyltriphenylphosphonium bromide (255 g, 0.714 m) in THF (2.50 L) cooled with an ice bath. The resultant yellow colored suspension was stirred for 30 minutes at ice bath temperature and then cooled to −78° C. A total of 2-fluoro-4-methoxyacetophenone (100 g, 0.595 m) in THF (200 ml) was added dropwise and stirred at −78° C. for 1.5 hours. Reaction mixture was allowed to warm to room temperature for one hour, quenched with acetic acid (˜80 ml) where color change was observed from yellow to off white and stirred for 30 minutes (pH˜7)(slight exotherm noted). The mixture was concentrated to a slush, diluted with 7:2 hexane:ethyl acetate, and was allowed to sit overnight. Solids were removed by filtration and the filtrate was concentrated to yellow oil. The title compound was obtained after flash column using 9:1 hexane:ethyl as the eluant.

1. temperaturecooled with an ice bath
2. stirringstirred at −78° C. for 1.5 hours
3. customReaction mixture
4. temperatureto warm to room temperature for one hour
5. customquenched with acetic acid (˜80 ml) where color change
6. stirringstirred for 30 minutes (pH˜7)(slight exotherm noted)
7. concentrationThe mixture was concentrated to a slush
8. additiondiluted with 7:2 hexane
9. waitto sit overnight
10. customSolids were removed by filtration
11. concentrationthe filtrate was concentrated to yellow oil

ORD record

ord-834b1594bf9d436b92091c03d408e084

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08735435B2