Carbamate → HCID 12085276, compound

Participants

Reaction Steps

To a solution of 186 mg of the above tert-butyl carbamate (0.55 mmol, 1 equiv.) in 1.6 mL anhydrous tert-butanol was added 52 uL of pyridine-3-carboxaldehyde (0.55 mmol, 1 equiv.) and 1.65 mL potassium tert-butoxide solution (1.0 M, 1.32 mmol, 3 equiv.). The mixture was heated to reflux overnight, then cooled. MeOH (5 mL) and HCl solution in dioxane (4.0 M) were added until pH˜1, the reaction was then stirred for 1.5 h at ambient temperature. The mixture was then quenched with saturated NaHCO3 aqueous solution and extracted with EtOAc (2×50 mL). The aqueous layer was treated with 4 N NaOH aqueous solution until pH˜12 and extracted 2 more times. The combined organic extracts were washed with brine, dried (MgSO4), filtered and concentrated to afford a mixture of crude products, including naphthylamine still protected as the carbamate. The residue was therefore taken up in dichloromethane (3 mL), treated with 2 mL TFA and left stirring over a weekend at ambient temperature. The mixture was quenched and neutralized with saturated aqueous NaHCO3, extracted with dichloromethane (3×50 mL), dried (MgSO4) and filtered. The volatiles were removed in vacuo and the crude product purified by column chromatography on SiO2 using 50 to 100% EtOAc in hexane eluent mixtures giving 35 mg (0.11 mmol, 20% of theoretical yield) title compound.

Provenance & Evidence