2-Bromopropane → 2-(3,4-Dimethoxyphenyl)-3-methylbutanenitrile

Temperature

-30 °C

To a solution of 9.99 g (56.4 mmol) of (3,4-Dimethoxyphenyl)acetonitrile in 141 mL of tetrahydrofuran (THF) at −30° C., was slowly added 56.4 mL (56.4 mmol) of sodium bis(trimethylsilyl)amide (NaHMDS, 1.0 M in THF). The mixture was stirred at −30° C. for 10 minutes and 10.6 mL (113.0 mmol) of 2-bromopropane was added. The mixture was heated to reflux for 2 hours (h) then left at 22° C. for about 16 h. A saturated aqueous solution of NH4Cl was added and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried (Na2SO4), filtered and evaporated. The residue was purified by flash chromatography on silica gel eluting first with hexane and then gradually increasing to 15% ethyl acetate/hexane to give 2-(3,4-dimethoxyphenyl)-3-methylbutanenitrile as an oil.

1. customat −30° C.
2. temperatureThe mixture was heated
3. temperatureto reflux for 2 hours (h)
4. waitthen left at 22° C. for about 16 h
5. extractionthe mixture was extracted with ethyl acetate
6. washThe organic layer was washed with brine
7. dry with materialdried (Na2SO4)
8. filtrationfiltered
9. customevaporated
10. customThe residue was purified by flash chromatography on silica gel eluting first with hexane
11. temperaturegradually increasing to 15% ethyl acetate/hexane

ORD record

ord-1de0264fd88043fa95c95fd18dd6fde3

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09227918B2