Dichloromethane → HCID 86716089, compound

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. aluminum block temp) for 10 min, and the resulting homogeneous yellow solution was cooled on 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 under ambient conditions for ˜5-10 min at which point exothermic POCl3 hydrolysis commenced (ice bath cooling), and was then stirred at room temperature for another 30 min. 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 on an ice bath
2. temperaturethe mixture was refluxed for 2 hours
3. temperature(ice bath cooling)
4. stirringwas then stirred at room temperature for another 30 min
5. extractionThe light yellow aqueous layer was extracted with DCM (1×30 mL)
6. dry with materialthe combined dark homogeneous organic layers were dried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated with silica gel
9. customwas dry load flash
10. customchromatographed with a 20% DCM/heptane to 100% DCM gradient

ORD record

ord-b76b3aae495f4389b5b0b131b33e8525

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09309222B2