Hydrochloric Acid → 4-Chloro-α,α-dimethylbenzenepropanenitrile

To a solution of lithium diisopropylamide (11.0 mL, 21.9 mmol, 2 Min tetrahydrofuran, Aldrich) in tetrahydrofuran (100 mL) was added isobutyronitrile (2.0 mL, 21.9 mmol) at 0-5° C. After 30 minutes of stirring, a solution of 1-(bromomethyl)-4-chlorobenzene (3.0 g, 14.6 mmol) in tetrahydrofuran (10 mL) was added at the same temperature. After stirring at room temperature for 2 hours, the reaction mixture was treated with 10% hydrochloric acid (50 mL), and concentrated under reduced pressure to remove tetrahydrofuran. The concentrate was extracted with ethyl acetate (3×50 mL). The combined organic extracts were washed successively with aqueous NaHCO3 (50 mL) and brine (50 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was then purified by column chromatography using an Analogix® Intelliflash 280™ (SiO2, 0-30% of ethyl acetate in hexanes) to obtain the titled compound. MS (DCI+) m/z 211 (M+NH4)+.

1. stirringAfter stirring at room temperature for 2 hours
2. concentrationconcentrated under reduced pressure
3. customto remove tetrahydrofuran
4. extractionThe concentrate was extracted with ethyl acetate (3×50 mL)
5. washThe combined organic extracts were washed successively with aqueous NaHCO3 (50 mL) and brine (50 mL)
6. dry with materialdried over anhydrous Na2SO4
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customThe residue was then purified by column chromatography

ORD record

ord-d1b9c9bb6acb42d4a3a6d09ecc6f2db0

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08507493B2