Dichloromethane → HCID 86716089, compound

Temperature

130 °C

A mixture of 2-phenylmalonic acid (7.62 g, 42.3 mmol) and POCl3 (32.8 mL, 352 mmol) was stirred at reflux (130° C.) for 10 minutes, and the resulting homogeneous yellow solution was cooled in an ice bath. 4-Bromo-2-methylaniline (6.56 g, 35.2 mmol) was added in one portion and the mixture was refluxed for 2 hours. The dark solution was allowed to cool to room temperature and was diluted with DCM (70 mL) and ice (100 mL), and stirred at room temperature for ˜5-10 minutes at which point exothermic POCl3 hydrolysis commenced (ice bath cooling), and was then stirred at room temperature for another 30 minutes. The light yellow aqueous layer was extracted with DCM (1×30 mL), and the combined dark homogeneous organic layers were dried (Na2SO4), filtered, and concentrated with silica gel. The silica-adsorbed residue was dry load flash chromatographed with a 20% DCM/heptane to 100% DCM gradient to provide the title compound as an off-white solid.

1. temperaturethe resulting homogeneous yellow solution was cooled in an ice bath
2. temperaturethe mixture was refluxed for 2 hours
3. temperatureto cool to room temperature
4. temperature(ice bath cooling)
5. stirringwas then stirred at room temperature for another 30 minutes
6. extractionThe light yellow aqueous layer was extracted with DCM (1×30 mL)
7. dry with materialthe combined dark homogeneous organic layers were dried (Na2SO4)
8. filtrationfiltered
9. concentrationconcentrated with silica gel
10. customThe silica-adsorbed residue was dry load flash
11. customchromatographed with a 20% DCM/heptane to 100% DCM gradient

ORD record

ord-71401c4fd9794397a6576fb3a73748a6

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09403816B2