Acetate → HCID 89781946, compound

Temperature

100 °C

A mixture of Pd(PPh3)4 (608 mg, 0.53 mmol), tributyl(1-ethoxyvinyl)tin (3.91 mL, 11.57 mmol), methyl 8-bromoquinoline-2-carboxylate (2.80 g, 10.52 mmol), and toluene (50 mL) was heated under argon at 100° C. for 18 h. The mixture was then concentrated under reduced pressure and adsorbed onto silica gel. Column chromatography (silica gel, 10-100% EtOAc in hexanes) afforded a mixture of vinyl ether (M+1=258.0) and the desired acetate. This mixture was dissolved in THF (40 mL), the solution was cooled to 0° C., 10 drops of 1N HCl were added, and the solution was stirred at 0° C. for 5 min. EtOAc (100 mL) was added and the resulting solution was washed successively with 1N NaOH (20 mL), water (40 mL) and brine (40 mL). Significant product remained in the aq. layer and was extracted with 25% IPA in CHCl3. The combined organic layers were dried over MgSO4, filtered, and concentrated to give methyl 8-acetylquinoline-2-carboxylate (1.98 g, 8.64 mmol, 82% yield) as a tan solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 8.69 (d, J=8.4 Hz, 1H), 8.27 (dd, J=8.2, 1.4 Hz, 1H), 8.20 (d, J=8.4 Hz, 1H), 8.00 (dd, J=7.2, 1.4 Hz, 1H), 7.79-7.86 (m, 1H), 3.98 (s, 3H), 2.92 (s, 3H). m/z (ESI, +ve ion) 230.0 (M+H)+.

1. concentrationThe mixture was then concentrated under reduced pressure
2. customColumn chromatography (silica gel, 10-100% EtOAc in hexanes) afforded
3. temperaturethe solution was cooled to 0° C.
4. washthe resulting solution was washed successively with 1N NaOH (20 mL), water (40 mL) and brine (40 mL)
5. extractionwas extracted with 25% IPA in CHCl3
6. dry with materialThe combined organic layers were dried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated

ORD record

ord-cfc5e650ac334339ac860a4b28eda408

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09394297B2