Dimethylformamide → 4-Cyclobutyl-5-formyl-2-methylbenzoic acid

Temperature

-78 °C

Into a three neck round-bottom flask, which was purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 4-cyclobutyl-5-iodo-2-methylbenzoic acid (compound 230.1, 5.00 g, 12.7 mmol, 1.00 equiv, 80%) in a solvent mixture of tetrahydrofuran and Et2O (50/50 mL). This was followed by the addition of butyllithium (15 mL, 2.50 equiv, 95%) dropwise with stirring at −78° C. To this was added N,N-dimethylformamide (2.50 g, 32.5 mmol, 2.00 equiv). The resulting solution was stirred for 1 h at −78° C. and then carefully quenched by slow addition of 50 mL of NH4Cl (aq.). The pH was adjusted to 1-2 with hydrogen chloride (6 M). The resulting solution was diluted with 100 mL of ethyl acetate, then washed with 4×50 mL of brine. The organic layer was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified using silica gel column chromatography with ethyl acetate/petroleum ether (1:1) as eluent to furnish 1.62 g (41%) of 4-cyclobutyl-5-formyl-2-methylbenzoic acid as a white solid.

1. customInto a three neck round-bottom flask, which was purged
2. temperaturemaintained with an inert atmosphere of nitrogen
3. stirringThe resulting solution was stirred for 1 h at −78° C.
4. customcarefully quenched by slow addition of 50 mL of NH4Cl (aq.)
5. additionThe resulting solution was diluted with 100 mL of ethyl acetate
6. washwashed with 4×50 mL of brine
7. dry with materialThe organic layer was dried over anhydrous sodium sulfate
8. concentrationconcentrated under vacuum
9. customThe residue was purified

ORD record

ord-adecb6686925474ea717627b8f15f389

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08871790B2