Hydrochloric Acid → Methyl 3-acetyl-4-Methylbenzoate

Temperature

120 °C

Into a 250-mL round-bottom flask, which was purged and maintained with an inert atmosphere of nitrogen, was placed a mixture of methyl 3-iodo-4-methylbenzoate (compound 5.3, 4.50 g, 16.3 mmol), 1-(vinyloxy)butane (4.21 mL, 32.6 mmol), TEA (4.53 mL, 32.5 mmol), 1,3-bis(diphenylphosphino)propane (672 mg, 1.63 mmol) and Pd(OAc)2 (349 mg, 1.55 mmol) in DMSO (50 mL). The mixture was stirred for 12 hours at 120° C., then cooled to room temperature. The pH was adjusted to 1-2 with aqueous hydrogen chloride (2 M) and stirred for 1 hour. The aqueous phase was extracted with ethyl acetate (3×200 mL) and the combined organic layers were washed with water (100 mL), then brine (3×100 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography with ethyl acetate/petroleum ether (1:50) as the eluent to yield 1.45 g (46%) of the title compound as a yellow solid.

1. customInto a 250-mL round-bottom flask, which was purged
2. temperaturemaintained with an inert atmosphere of nitrogen
3. temperaturecooled to room temperature
4. stirringstirred for 1 hour
5. extractionThe aqueous phase was extracted with ethyl acetate (3×200 mL)
6. washthe combined organic layers were washed with water (100 mL)
7. dry with materialbrine (3×100 mL), dried (Na2SO4)
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customThe residue was purified by silica gel column chromatography with ethyl acetate/petroleum ether (1:50) as the eluent

ORD record

ord-775d531fe3c447eca8e809229d9fac04

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09428502B2