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 62.1, 5.00 g, 80%, 12.7 mmol) in a solvent mixture of tetrahydrofuran and Et2O (50 mL/50 mL). The solution was cooled to −78° C. then n-butyllithium (15 mL, 2.5 M in hexanes) was added drop-wise with stirring. N,N-Dimethylformamide (2.64 mL, 34.2 mmol) was added and the resulting mixture was stirred for 1 h at −78° C., then carefully quenched by slow addition of aqueous NH4Cl (sat., 50 mL). The pH was adjusted to 1-2 with aqueous hydrogen chloride (6 M), then diluted with ethyl acetate (100 mL) and washed with brine (4×50 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified using silica gel column chromatography with ethyl acetate/petroleum ether (1:1) as the eluent to furnish 1.62 g (41%) of the title compound 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 mixture was stirred for 1 h at −78° C.
4. customcarefully quenched by slow addition of aqueous NH4Cl (sat., 50 mL)
5. additiondiluted with ethyl acetate (100 mL)
6. washwashed with brine (4×50 mL)
7. dry with materialThe organic layer was dried over anhydrous sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customThe residue was purified

ORD record

ord-5a1c38befcf24801b1b6f7ccf1a1fa52

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09428502B2