Acetonitrile → 3-(3-Bromophenyl)-3-hydroxypropanenitrile

Temperature

-78 °C

To a −78° C. solution of acetonitrile (1.05 mL, 20 mmol) in anhydrous THF (25 mL) under argon, was added lithium diisopropylamide (11 mL of a 2 M solution in THF, 22 mmol) dropwise. The resulting mixture was stirred at −78° C. for 15 min. A solution of 3-bromobenzaldehyde (22) (2.78 g, 15 mmol) in anhydrous THF (10 mL) was added dropwise. The reaction mixture was allowed to warm to room temperature, then concentrated under reduced pressure and diluted with EtOAc (75 mL). The solution was washed with water (50 mL) and brine (50 mL), dried over Na2SO4 and concentrated under reduced pressure. Purification by flash chromatography (20 to 100% EtOAc-hexanes gradient) gave 3-(3-bromophenyl)-3-hydroxypropanenitrile (23) as a light yellow oil. Yield (2.75 g, 81%): 1H NMR (400 MHz, DMSO-d6) δ 7.60 (t, J=1.6 Hz, 1H), 7.46 (ddd, J=7.6, 2.0, 1.2 Hz, 1H), 7.40 (dd, J=7.6, 2.0 Hz, 1H), 7.31 (t, J=7.6 Hz, 1H), 6.05 (d, J=4.8 Hz, 1H), 4.87-4.92 (m, 1H), 2.94-2.80 (m, 2H).

1. temperatureto warm to room temperature
2. concentrationconcentrated under reduced pressure
3. additiondiluted with EtOAc (75 mL)
4. washThe solution was washed with water (50 mL) and brine (50 mL)
5. dry with materialdried over Na2SO4
6. concentrationconcentrated under reduced pressure
7. customPurification by flash chromatography (20 to 100% EtOAc-hexanes gradient)

ORD record

ord-a653cc801e7b4ae6a48d0ae77deda327

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08492589B2