Hydrochloric Acid → 2-{[2-(2-Benzo[b]thiophen-5-ylethoxy)ethyl]amino}-1-propanol

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Reaction Steps

In 10 mL of methylene chloride is dissolved 1.0 g of 2-(2-benzo[b]thiophen-5-ylethoxy)-acetic acid. At an ice-cooled temperature, 0.41 mL of oxalyl chloride and 0.1 mL of N,N-dimethylformamide are added to the solution obtained above, and the mixture is stirred at ambient temperature for 1.5 hours. After cooling the mixture to −50° C., 0.41 mL of DL-alaninol and 1.77 mL of triethylamine are dropwise added, and the mixture thus formed is stirred at ambient temperature for 4 hours. Ice water is added to the reaction mixture, pH is adjusted to 1 with 6 mol/L hydrochloric acid, and the organic layer is separated. The organic layer is washed with saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and the solvent is distilled off under reduced pressure. The residue thus obtained is dissolved in 10 mL of tetrahydrofuran and cooled with ice, to which is dropwise added 16.9 mL of 1 mol/L solution of borane-tetrahydrofuran complex in tetrahydrofuran. The mixture thus obtained is stirred at ambient temperature for 13 hours. The reaction mixture is acidified with 5.6 mL of 6 mol/L hydrochloric acid and heated under reflux for one hour. After cooling the reaction mixture, the solvent is distilled off under reduced pressure, water and ethyl acetate are added to the residue, and the aqueous layer is separated. Ethyl acetate is added to the aqueous layer, pH is adjusted to 9.5 with 50% aqueous solution of sodium hydroxide, and the organic layer is separated. The organic layer thus obtained is washed with saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, the solvent is distilled off under reduced pressure, and an oily residue thus obtained is purified by column chromatography (eluent: chloroform:methanol=40:1 to 30:1) to obtain 0.80 g of 2-{[2-(2-benzo[b]thiophen-5-ylethoxy)ethyl]amino}-1-propanol as a light yellow-colored oily product.

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