1-Chloro-2-naphthol

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 400 mg (2.24 mmol) of 1-chloronaphthalen-2-ol in 3 mL of MeOH, HBr (purum p.a., ≧62%, 270 μL) and H2O2 (50 wt. % in water solution, 27 μL) were added. The resulting mixture was heated at 40° C. and stirred overnight. The mixture was quenched with water (10 mL) and extracted with ethyl acetate (10 mL×2). The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to afford 6-bromo-1-chloronaphthalen-2-ol as pale yellow solid which was used in the next step without further purification. HPLC-MS (ESI+): m/z 258.51 [M+H+]. The mixture was quenched with water (10 mL) extracted with ethyl acetate (10 mL×2) The organic layer was dried over anhydrous sodium sulfate filtered concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1-chloronaphthalen-2-ol (1.5 mmol) and Cs2CO3 (3 mmol) in acetonitrile was added tert-butyl (1-bromo-2-methylpropan-2-yl)carbamate (3 mmol). The resulting mixture was heated at reflux overnight. After TLC control (n-hexane/ethyl acetate 7:3) showed the disappearance of 1-chloronaphthalen-2-ol, solvent was evaporated in vacuo and the residue was dissolved in 15 mL of ethyl acetate and washed with water (3×5 mL), brine (10 mL) and dried over Na2SO4. The evaporation of solvent afforded tert-butyl {1-[(1-chloronaphthalen-2-yl)oxy]-2-methylpropan-2-yl}carbamate as a pale oil (51% yield) which was dissolved in 5 mL of 4 M HCl solution in dioxane. The resulting mixture was stirred at room temperature for 18 h. After HPLC-MS control, the solvent was distilled off and the residue was dissolved in dichloromethane and wash 2 times with NaOH 1N to afford 1-[(1-chloronaphthalen-2-yl)oxy]-2-methylpropan-2-amine as a pale oil. The resulting mixture was heated at reflux overnight was evaporated in vacuo the residue was dissolved in 15 mL of ethyl acetate washed with water (3×5 mL), brine (10 mL) dried over Na2SO4 The evaporation of solvent

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1-chloronaphthalen-2-ol (1.68 mmol) and K2CO3 (3.36 mmol) in acetone was added tert-butyl (2-bromoethyl)carbamate (1.85 mmol). The resulting mixture was heated at reflux overnight. After TLC control (n-hexane/ethyl acetate 7:3) showed the disappearance of 1-chloronaphthalen-2-ol, solvent was evaporated in vacuo and the residue was dissolved in 15 mL of ethyl acetate and washed with water (3×5 mL), brine (10 mL) and dried over Na2SO4. The evaporation of solvent afforded tert-butyl {2-[(1-chloronaphthalen-2-yl)oxy]ethyl}carbamate as a grey solid (77% yield) which was used without further purification. The resulting mixture was heated at reflux overnight was evaporated in vacuo the residue was dissolved in 15 mL of ethyl acetate washed with water (3×5 mL), brine (10 mL) dried over Na2SO4 The evaporation of solvent

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a cooled (0-5° C.) solution of N-chlorosuccinimide (1.4 g, 10.4 mmol) in 100 mL of CH2Cl2, ZrCl4 (0.122 g, 5% mol) was added followed by 1.5 g (10.4 mmol) of naphthalen-2-ol. The mixture was stirred for 18 h at room temperature until the complete disappearance of the starting material as judged by TLC and GC analysis. The mixture was quenched with saturated NH4Cl aqueous solution (30 mL) and transferred to a separatory funnel. The two phases were separated and the organic one was washed with water (3×10 mL), dried over Na2SO4 and evaporated under vacuum to give yellow oil. The crude was purified by flash cromatography (petroleum ether/ethyl acetate 85:15) to afford 1-chloronaphtalen-2-ol (1.4 gr, 78% yield), as white solid. was added The mixture was quenched with saturated NH4Cl aqueous solution (30 mL) transferred to a separatory funnel The two phases were separated the organic one was washed with water (3×10 mL) dried over Na2SO4 evaporated under vacuum to give yellow oil The crude was purified by flash cromatography (petroleum ether/ethyl acetate 85:15)