Triethylamine → 3-Aminonaphthalen-1-ol

Participants

Reaction Steps

A solution of 4-methoxy-2-naphthylamine (230 mg, 1.33 mmol) in glacial acetic acid (9.6 mL) and hydrobromic acid in water (16 mL, 48%) was refluxed under N2 for 4 h. A small amount of sample (0.1 mL) was diluted with ethyl acetate (0.5 mL), and then water (0.5 mL) and triethylamine (0.1 mL) were added. TLC (20:1 DCM/methanol) of the organic layer showed no starting material and a new much lower spot (Rf=0.1). The solvent was removed under reduced pressure and the product was dried under vaccum to yield the intermediate 4-hydroxy-2-naphthylamine which was used for the next step without any purification. To a solution of 4-hydroxy-2-naphthylamine in dioxane (10 mL) was added TEA (1 mL) and di-tert-butyl dicarbonate (1.149 g, 5.27 mmol). The reaction mixture was refluxed under N2 for 4 h. TLC (4:1 hexane/ethyl acetate) showed no starting material and a new higher spot (Rf=0.55). The reaction mixture was diluted with ethyl acetate (50 mL) and washed with water. The aqueous layer was extracted with ethyl acetate (2×50 mL) and the organics were combined and washed with brine. The organics were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to yield N-(tert-butyloxycarnonyl)-4-O-(tert-butyloxycarbonyl)-2-naphthylamine (2, 80% yield) as oil. To a solution of compound 2 in acetone (10 mL) was added NaOH solution in water (10 mL, 1 M). The reaction mixture was stirred at room temperature for overnight. TLC (4:1 Hexane/Ethyl acetate) showed no starting material and a new lower spot. The reaction mixture was extracted with ethyl acetate (50 mL) and washed with water. The aqueous layer was extracted with ethyl acetate (2×50 mL) and the organics were washed with brine, dried over anhydrous Na2SO4 and concentrated. The residue was purified on 10 g silica gel column with 10-20% ethyl acetate in hexane to yield compound 3 (181 mg, 53%) as an oil.

Provenance & Evidence