Water → HCID 136121342, compound

Participants

Reaction Steps

To a cooled (0-5° C.) suspension of 2-(4-chloro-7-methylquinazolin-2-yl)phenol (50.2 g, 186 mmol) in dichloromethane (200 mL) was slowly added a solution of tert-butyl piperidin-4-ylcarbamate (39.0 g, 195 mmol) and triethylamine (56 mL, 390 mmol) in dichloromethane (200 mL). The resulting mixture was stirred overnight at room temperature. Water (400 ml) was added, and the layers were separated. The aqueous layer was extracted with dichloromethane (2×200 mL), and the combined organic layers were dried over sodium sulfate, filtered, and evaporated to dryness under reduced pressure. The residue was purified by column chromatography (SiO2, eluent: dichloromethane/heptanes 4:6-1:0). Two fractions were obtained: 38.7 g of tert-butyl 1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperidin-4-ylcarbamate as a yellow solid, and a less pure fraction (26.1 g) that was purified by recrystallization from methanol to yield tert-butyl 1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperidin-4-ylcarbamate. Both fractions were combined (17.0 g, 69%).

Provenance & Evidence