Tetrahydrofuran → 4-(2-Methoxyethoxy)pyridin-2-amine

Participants

Reaction Conditions

Reaction Steps

A steady stream of nitrogen was passed through a mixture of 2-chloro-4-(2-methoxyethoxy)pyridine (50.1 g, 267 mmol), Pd2dba3 (4.89 g, 5.34 mmol), XPHOS (5.09 g, 10.7 mmol) and tetrahydrofuran (445 ml) for 10 minutes. To the resulting degassed mixture was added lithium bis(trimethylsilyl)amide (561 ml, 561 mmol). After addition, the resulting mixture was heated to 60° C. for 18 hours. The reaction was cooled to ambient temperature and diluted with 1 N hydrochloric acid (200 mL). The resulting solution was washed twice with 500 ml of methyl-tert-butyl ether. The pH of the aqueous layer was adjusted to 11 with 6 N NaOH and extracted with dichloromethane. The combined organic layers were dried over MgSO4 and concentrated under reduced pressure to yield title compound (35 g) MS APCI (+) m/z 169 (M+1) detected.

Provenance & Evidence