Allyl bromide → 4-(2-(4-Methoxyphenyl)pent-4-enoyl)-3-methylbenzonitrile

Temperature

-78 °C

To a solution of A-7 (4-(2-(4-methoxyphenyl)acetyl)-3-methylbenzonitrile) (19 g, 71.6 mmol) in anhydrous tetrahydrofuran (200 mL) was added dropwise lithium hexamethyldisilazide (LiHMDS) (86 mL, 1 mol/L in THF) at −78° C. under nitrogen, and the reaction mixture was stirred at −78° C. for 30 min. A solution of 3-bromo-propene (10.4 g, 86 mmol) in anhydrous tetrahydrofuran (70 mL) was added dropwise into the mixture, and the resulting mixture was warmed to room temperature and stirred overnight. The reaction was quenched by the addition of saturated aqueous ammonium chloride solution (200 mL), and extracted with ethyl acetate (100 mL×3). The combined organic layers were washed with brine (200 mL), dried over anhydrous sodium sulfate (10 g), evaporated, and purified on silica gel column (petroleum ether/ethyl acetate=25:1) to give A-8 (4-(2-(4-methoxyphenyl)pent-4-enoyl)-3-methylbenzonitrile) (7.7 g, yield 35.2%) as an oil. 1H NMR (CDCl3 400 MHZ): δ 7.36 (m, 3H), 7.01 (d, J=8.4 Hz, 2H), 6.74 (d, J=8.4 Hz, 2H), 5.72-5.62 (m, 1H), 5.04-4.93 (m, 2H), 4.20-4.17 (m, 1H), 3.69 (s, 3H), 2.92-2.85 (m, 1H), 2.52-2.40 (m, 1H), 2.16 (s, 3H).

1. temperaturethe resulting mixture was warmed to room temperature
2. stirringstirred overnight
3. customThe reaction was quenched by the addition of saturated aqueous ammonium chloride solution (200 mL)
4. extractionextracted with ethyl acetate (100 mL×3)
5. washThe combined organic layers were washed with brine (200 mL)
6. dry with materialdried over anhydrous sodium sulfate (10 g)
7. customevaporated
8. custompurified on silica gel column (petroleum ether/ethyl acetate=25:1)

ORD record

ord-a0e6484909b147ee81c9a2160223ace5

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08642628B2