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

Temperature

-78 °C

To a solution of 4-cyclobutyl-5-iodo-2-methylbenzoic acid (compound 230.1, 3.00 g, 9.49 mmol, 1.00 equiv) in THF (40 mL) under nitrogen at −78° C. was added dropwise n-BuLi (9.5 mL, 2.50 equiv, 2.5 M in THF). After 10 minutes, a solution of dimethyl carbonate (2.56 g, 28.4 mmol, 3.00 equiv) in THF (10 mL) was added dropwise at −78° C. The resulting solution was stirred for 1 h at −78° C., then carefully quenched by slow addition of 50 mL of water. The pH was adjusted to ˜4 with hydrogen chloride (aq., 1 M). The resulting mixture was extracted with 2×80 mL of ethyl acetate, the combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified using silica gel column chromatography with ethyl acetate/petroleum ether (1:10-1:2) as eluent to furnish 1.30 g (55%) of 4-cyclobutyl-5-(methoxycarbonyl)-2-methylbenzoic acid as a white solid.

1. customcarefully quenched by slow addition of 50 mL of water
2. extractionThe resulting mixture was extracted with 2×80 mL of ethyl acetate
3. dry with materialthe combined organic layers were dried over anhydrous sodium sulfate
4. concentrationconcentrated in vacuo
5. customThe residue was purified

ORD record

ord-ded5398d703d4137b5aa051601d9354b

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08871790B2