ethyl 2-naphthalen-1-yloxyacetate

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred mixture of ethyl 2-(naphthalen-1-yloxy)acetate (150 mg, 0.641 mmol) in EtOH (2 mL) was added 1-amino-3-(3,4-dihydroisoquinolin-2(1H)-yl)propan-2-ol (132 mg, 0.641 mmol). The mixture was stirred at 120° C. for 30 minutes under microwave mediated heating. After evaporation of the solvent, the reaction mixture was purified by prep-HPLC to afford the desired product (64 mg, Yield 25%). 1H NMR (400 MHz, METHANOL-d4) δ=8.41-8.31 (m, 1H), 7.90-7.80 (m, 1H), 7.58-7.46 (m, 3H), 7.44-7.35 (m, 1H), 7.18-6.95 (m, 5H), 6.91 (d, J=7.8 Hz, 1H), 4.76 (s, 2H), 4.05 (quin, J=6.0 Hz, 1H), 3.72-3.59 (m, 2H), 3.56-3.48 (m, 1H), 3.41 (dd, J=6.5, 13.6 Hz, 1H), 2.93-2.83 (m, 2H), 2.80-2.72 (m, 2H), 2.59-2.52 (m, 2H). LCMS (m/z): 391.2 (M+1). After evaporation of the solvent the reaction mixture was purified by prep-HPLC

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred mixture of naphthalen-1-ol (196 mg, 1.35 mmol) in MeCN (5 mL) was added ethyl bromoacetate (269 mg, 1.62 mmol) and K2CO3 (372 mg, 2.70 mmol). The mixture was stirred at 80° C. for 4 hours. The mixture was filtered and the filtrate concentrated. The residue was used directly for the next step without further purification (300 mg, Yield 95%). The mixture was filtered the filtrate concentrated The residue was used directly for the next step without further purification (300 mg, Yield 95%)

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

Procedure: 15 g of the ester obtained according to (a) are dissolved in 300 ml ethanol; after addition of 7.6 g potassium carbonate in solution in 25 ml water, the mixture is refluxed for 17 hours and the alcohol removed under reduced pressure. The residue is purified by dissolution in water; the final product is extracted from the aqueous phase after acidification. 12 g of the acid which, after recrystallisation from dichloroethane, melts at 177° C. are obtained. the mixture is refluxed for 17 hours the alcohol removed under reduced pressure The residue is purified by dissolution in water the final product is extracted from the aqueous phase after acidification 12 g of the acid which, after recrystallisation from dichloroethane, melts at 177° C. are obtained

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 483 g ethyl 1-naphthyloxyacetate and 308 g thiophene-2-carboxylic acid chloride was dissolved in 3.570 l. methylene chloride. While the mixture is being maintained at about -10° C., 291 g aluminium chloride are introduced slowly; after 2 hours at -10° C., the mixture is brought back to 25° C. and the stirring maintained for 12 hours. The mixture is then poured into 2 Kg iced water, the organic phase decanted off, washed with dilute aqueous sodium hydroxide solution then water and the solvent evaporated. 562 g of the ester are thus obtained. After recrystallisation from isopropyl ether, it melts at 79° C. is brought back to 25° C. the stirring maintained for 12 hours the organic phase decanted off washed with dilute aqueous sodium hydroxide solution water and the solvent evaporated

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

Procedure: 432 g 1-naphthol, 602 g ethyl 2-bromoacetate, 276 g potassium carbonate and 2.160 l. ethanol are refluxed for 18 hours, the precipitate filtered, the solvent evaporated under reduced pressure and the residue recrystallized from petroleum ether. The ester, which melts at 52° C., is obtained with an 80% yield. the precipitate filtered the solvent evaporated under reduced pressure the residue recrystallized from petroleum ether

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred mixture of ethyl 2-(naphthalen-1-yloxy)acetate (150 mg, 0.641 mmol) in EtOH (2 mL) was added 1-amino-3-(3,4-dihydroisoquinolin-2(1H)-yl)propan-2-ol (132 mg, 0.641 mmol). The mixture was stirred at 120° C. for 30 minutes under microwave mediated heating. After evaporation of the solvent, the reaction mixture was purified by prep-HPLC to afford the desired product (64 mg, Yield 25%). 1H NMR (400 MHz, METHANOL-d4) δ=8.41-8.31 (m, 1H), 7.90-7.80 (m, 1H), 7.58-7.46 (m, 3H), 7.44-7.35 (m, 1H), 7.18-6.95 (m, 5H), 6.91 (d, J=7.8 Hz, 1H), 4.76 (s, 2H), 4.05 (quin, J=6.0 Hz, 1H), 3.72-3.59 (m, 2H), 3.56-3.48 (m, 1H), 3.41 (dd, J=6.5, 13.6 Hz, 1H), 2.93-2.83 (m, 2H), 2.80-2.72 (m, 2H), 2.59-2.52 (m, 2H). LCMS (m/z): 391.2 (M+1). After evaporation of the solvent the reaction mixture was purified by prep-HPLC

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred mixture of naphthalen-1-ol (196 mg, 1.35 mmol) in MeCN (5 mL) was added ethyl bromoacetate (269 mg, 1.62 mmol) and K2CO3 (372 mg, 2.70 mmol). The mixture was stirred at 80° C. for 4 hours. The mixture was filtered and the filtrate concentrated. The residue was used directly for the next step without further purification (300 mg, Yield 95%). The mixture was filtered the filtrate concentrated The residue was used directly for the next step without further purification (300 mg, Yield 95%)