反应详情

温度

100 °C

To a round-bottom flask, which was purged and maintained with a nitrogen atmosphere, was added a solution of methyl 4-cyclobutyl-2-ethyl-5-iodobenzoate (compound 181.4, 5.50 g, 16.0 mmol, 1.00 equiv) in N,N-dimethylformamide (150 mL). Zinc cyanide (2.78 g, 23.7 mmol, 1.50 equiv) and Pd(PPh3)4 (1.83 g, 1.59 mmol, 0.10 equiv) were added to the reaction mixture. The resulting solution was stirred at 100° C. for 15 h under nitrogen. After cooling to ambient temperature, the reaction was carefully quenched with 300 mL of FeSO4 (aq., sat.) and diluted with ethyl acetate. The resulting mixture was stirred vigorously then filtered through celite and washed with 1 M FeSO4, water, and ethyl acetate. The layers were separated and the aqueous phase was extracted with 2×300 mL of ethyl acetate. The combined organic layers were washed with 2×300 mL of brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was purified using silica gel column chromatography with ethyl acetate/petroleum ether (1:100-1:50) as eluent to furnish 3.20 g (82%) of methyl 5-cyano-4-cyclobutyl-2-ethylbenzoate as a light yellow oil.

1. customTo a round-bottom flask, which was purged
2. temperaturemaintained with a nitrogen atmosphere
3. temperatureAfter cooling to ambient temperature
4. customthe reaction was carefully quenched with 300 mL of FeSO4 (aq., sat.)
5. additiondiluted with ethyl acetate
6. stirringThe resulting mixture was stirred vigorously
7. filtrationthen filtered through celite
8. washwashed with 1 M FeSO4, water, and ethyl acetate
9. customThe layers were separated
10. extractionthe aqueous phase was extracted with 2×300 mL of ethyl acetate
11. washThe combined organic layers were washed with 2×300 mL of brine
12. dry with materialdried over anhydrous sodium sulfate
13. concentrationconcentrated in vacuo
14. customThe residue was purified