Pyridine → HCID 23093485, compound

Participants

Reaction Steps

To a solution of bis(trichloromethyl) carbonate (4.45 g) in tetrahydrofuran (50 mL) was added dropwise N-ethyldiisopropylamine (5.75 mL) under ice-cooling. After stirring for a while, a solution of 3-methoxypropanol obtained above (2.70 g) in tetrahydrofuran (15 mL) was added dropwise thereto. The reaction solution was stirred under ice-cooling for 30 minutes, and at room temperature for 1 day. The reaction solution was concentrated under reduced pressure, and to the residue was added dilute hydrochloric acid (50 mL), and extracted with ethyl acetate (80 mL). The ethyl acetate layer was washed with 0.2 N hydrochloric acid (30 mL) and saturated brine (30 mL), and dried over anhydrous magnesium sulfate. The solution was concentrated under reduced pressure to give 3-methoxypropyl chlorocarbonate (4.39 g). To a solution of tert-butyl 2-hydroxyethyl(methyl)carbamate (1.75 g) obtained in Reference Synthetic Example 1 in tetrahydrofuran (20 mL) was added pyridine (0.97 mL), then a solution of 3-methoxypropyl chlorocarbonate obtained above (1.83 g) in tetrahydrofuran (5 mL) was added dropwise thereto, and stirred at room temperature for 2 hrs. A solution of pyridine (0.65 mL) and 3-methoxypropyl chlorocarbonate (1.22 g) in tetrahydrofuran (5 mL) was further added, stirred for 1 hr, and the reaction solution was concentrated under reduced pressure. To the residue was added water (50 mL), and extracted with ethyl acetate (80 mL). The ethyl acetate layer was washed with 5% aqueous solution of citric acid (50 mL) and saturated saline (50 mL), and dried over anhydrous magnesium sulfate, followed by concentrating under reduced pressure. The residue was purified with silica gel column chromatography (eluted with ethyl acetate:hexane=1:9, then 3:7). The purified material (3.40 g) was dissolved in diethyl ether (5 mL), and added 4N hydrogen chloride-ethyl acetate solution (5 mL). After stirring at room temperature overnight, the reaction solution was concentrated under reduced pressure. By adding diethyl ether to crystallize, the title compound was obtained as colorless solid (2.06 g).

Provenance & Evidence