Dimethyl Carbonate → 4-Cyclobutyl-2-ethyl-5-(methoxycarbonyl)benzoic acid

Temperature

25 °C

To a solution of 4-cyclobutyl-2-ethyl-5-iodobenzoic acid (compound 215.3, 3.30 g, 10.0 mmol, 1.00 equiv) in THF (40 mL) was added n-BuLi (2.5 M, 9.50 mL, 2.38 equiv) dropwise at −78° C. under nitrogen atmosphere. The resulting solution was stirred for another 20 min at the same temperature, followed by the addition of a solution of dimethyl carbonate (2.70 g, 30.0 mmol, 3.00 equiv) in tetrahydrofuran (2 mL) dropwise. The reaction temperature was slowly raised to 25° C. and stirred for another 1 h, then slowly quenched with 50 mL of water. The pH was adjusted to ˜4 with HCl (aq., 1 M) and the resulting mixture was extracted with 100 mL of ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography with ethyl acetate/petroleum ether (1:3) as eluent to furnish 1.80 g (69%) of the desired product as a white solid.

1. stirringstirred for another 1 h
2. customslowly quenched with 50 mL of water
3. extractionthe resulting mixture was extracted with 100 mL of ethyl acetate
4. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
5. concentrationconcentrated in vacuo
6. customThe residue was purified by silica gel chromatography with ethyl acetate/petroleum ether (1:3) as eluent

ORD record

ord-ca11862a47934f618e979e7dca5691f4

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08871790B2