Ethyl bromoacetate → Ethyl 3-cyanopent-4-enoate

Temperature

-78 °C

n-Butyllithium (2.5 M in THF, 33 mL, 82 mmol) was added dropwise to a solution of diisopropylamine (9.0 g, 90 mmol) in THF at −78° C. The reaction mixture was stirred at −78° C. for 1 hour. To the mixture was added a solution of 3-butenenitrile (5.0 g, 74.6 mmol) in THF (30 mL) dropwise at −78° C. The resultant mixture was stirred at the temperature for 1 hour, then a solution of ethyl bromoacetate (13.7 g, 82.06 mmol) in THF (30 mL) was added dropwise at −78° C. to the reaction mixture. The reaction mixture was stirred at −78° C. for an additional 1 hour. The reaction mixture was poured into a solution of saturated aqueous ammonium chloride and extracted with tert-butyl methyl ether (3×300 mL). The organic layers were combined, dried over sodium sulfate, filtered, and concentrated under reduced pressure to afford the crude product residue. The crude product residue was purified by silica gel chromatography (ethyl acetate/petroleum ether) to afford ethyl 3-cyanopent-4-enoate as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 5.83-5.71 (m, 1H), 5.53-5.49 (m, 1H), 5.36-5.33 (m, 1H), 4.20 (q, J=7.2 Hz, 2H), 3.79-3.71 (m, 1H), 2.81-2.73 (m, 1H), 2.69-2.61 (m, 1H), 1.28 (t, J=7.2 Hz, 3H).

1. stirringThe reaction mixture was stirred at −78° C. for an additional 1 hour
2. extractionextracted with tert-butyl methyl ether (3×300 mL)
3. dry with materialdried over sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure
6. customto afford the crude product residue
7. customThe crude product residue was purified by silica gel chromatography (ethyl acetate/petroleum ether)

ORD record

ord-d581a04d91fb4943b9c7edad45b368c4

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09242984B2