Triethylamine → 4-Chloro-6-(1,1-dimethylethyl)pyrimidine

6-(1,1-Dimethylethyl)-4-pyrimidinol (Intermediate 9, 1.66 g, 10.91 mmol) was suspended in DCM (10 mL), treated with triethylamine (1.520 mL, 10.91 mmol), followed by phosphorus oxychloride (1.118 mL, 12.00 mmol) dropwise. An exotherm was observed. The resulting mixture was heated under reflux for 3 hours. LCMS indicates no desired product present and starting material remaining. The reaction mixture was allowed to cool to room temperature and evaporated under reduced pressure. The residue was treated with phosphorus oxychloride (5.08 mL, 54.5 mmol) and the resulting mixture was heated under reflux for 30 minutes. The reaction mixture was allowed to cool to room temperature, evaporated under reduced pressure and the residue was poured into 2M aqueous hydrochloric acid solution (10 mL). This solution was extracted with DCM (×2). The DCM layers were combined, dried under magnesium sulfate and evaporated under reduced pressure. The residue was purified by column chromatography (Biotage SP4) eluting with a gradient of 0-20% ethyl acetate and iso-hexane. Product containing fractions were combined and evaporated under reduced pressure to give the title compound as a colourless oil (1.17 g);

1. temperatureThe resulting mixture was heated
2. temperatureunder reflux for 3 hours

ORD record

ord-efa2a0049944493d97d8d22fd51fd42e

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08796283B2