Dimethylformamide → Methyl 5-cyano-4-cyclopropyl-2-methylbenzoate

Temperature

100 °C

To a solution of methyl 4-cyclopropyl-5-iodo-2-methylbenzoate (compound 142.2, 2.00 g, 6.01 mmol, 1.00 equiv, 95%) in DMF (16 mL) was added Zn(CN)2 (890 mg, 7.58 mmol, 1.27 equiv) and Pd(PPh3)4 (731 mg, 0.630 mmol, 0.11 equiv). The resulting solution was stirred at 100° C. under nitrogen overnight. After cooling to ambient temperature, the reaction was then quenched by the addition of 100 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 2×100 mL of ethyl acetate. The combined organic phases were dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified via silica gel column chromatography with ethyl acetate/petroleum ether (1/50) as eluent to yield 1.10 g (81%) of methyl 5-cyano-4-cyclopropyl-2-methylbenzoate as a light yellow oil.

1. temperatureAfter cooling to ambient temperature
2. customthe reaction was then quenched by the addition of 100 mL of FeSO4 (aq., sat.)
3. additiondiluted with ethyl acetate
4. stirringThe resulting mixture was stirred vigorously
5. filtrationthen filtered through celite
6. washwashed with 1 M FeSO4, water, and ethyl acetate
7. customThe layers were separated
8. extractionthe aqueous phase was extracted with 2×100 mL of ethyl acetate
9. dry with materialThe combined organic phases were dried over anhydrous sodium sulfate
10. concentrationconcentrated in vacuo
11. customThe residue was purified via silica gel column chromatography with ethyl acetate/petroleum ether (1/50) as eluent

ORD record

ord-4be2e89b9dd24c85a1f44c52da01ea3d

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08871790B2