Piperidin-4-ol → 2-[4-(4-Hydroxy-piperidin-1-yl)-2-methyl-phenyl]-8-oxa-2-aza-spiro[4.5]decan-1-one

Participants

Reaction Steps

An 25-mL round bottom flask containing a stir bar was charged with Pd2(dba)3 (00.01 equiv., 0.0154 mmol, 14 mg.), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl 1 (0.05 equiv., 0.077 mmol, 36.7 mg), 2-(4-bromo-2-methyl-phenyl)-8-oxa-aza-spiro[4.5]decan-1-one (0.50 g, 1.54 mmol, 1 equiv.), and sodium t-butoxide (2.5 equiv., 3.85 mmol, 370 mg.), and piperidin-4-ol (1.5 equiv., 2.3 mmol, 234 mg). The vial was capped with a rubber septum, evacuated and backfilled with N2. To this vial was introduced 8 mL of anhydrous toluene. The reaction was heated in an oil bath set at 90° C. for 2 h, allowed to cool down to room temperature and quenched with water (2 mL). The two layers were separated and the aqueous layer was extracted with DCM (3×10 mL). The combined DCM extracts were washed with sodium bicarbonate (50 mL), and brine (50 mL), dried (anhydrous potassium carbonate), filtered, and concentrated. The crude product was purified by a silica gel column to give 75.1 mg (14% yield) of the title compound as a light yellow solid after standing.

Provenance & Evidence