4-Amino-1-naphthol hydrochloride → 4-(2-Chloropyridin-4-yloxy)naphthalen-1-amine

Participants

Reaction Steps

To a stirred solution of 2-chloro-4-fluoropyridine (1.261 g, 9.58 mmol) and 4-amino-1-naphthol hydrochloride (2) (750 mg, 3.83 mmol) in NMP (40 mL), at −20° C., was added potassium tert-butoxide (1.290 g, 11.50 mmol). The reaction mixture was allowed to warm to RT. After 2.5 hr, the reaction mixture was diluted with water (100 mL) and extracted with EtOAc (100 mL then 2×80 mL). The combined organic extracts were washed with brine (150 mL), dried and evaporated in vacuo. The crude product was subjected to SCX capture and release eluting with 1% NH3 in MeOH solution and the solvent was removed in vacuo to give 4-(2-chloropyridin-4-yloxy)naphthalen-1-amine (3) (1.019 g, 92%) as a brown solid: m/z 271 (M+H)+ (ES+).

Provenance & Evidence