Pyridine → 2-Ethoxyethyl chloroformate

To a solution of bis(trichloromethyl) carbonate (2.97 g) in tetrahydrofuran (20 mL) was added dropwise a solution of 2-ethoxyethanol (1.80 g) in tetrahydrofuran (10 mL) under ice-cooling. Then, a solution of pyridine (2.43 mL) in tetrahydrofuran (10 mL) was added dropwise thereto, and stirred at room temperature for 2 hrs. The reaction solution was concentrated under reduced pressure, and to the residue was added water (50 mL), and extracted with ethyl acetate (50 mL). The ethyl acetate layer was washed with 0.2 N hydrochloric acid (20 mL) and saturated brine (50 mL), and dried over anhydrous magnesium sulfate. The solution was concentrated under reduced pressure to give 2-ethoxyethyl chlorocarbonate (1.29 g). To a solution of tert-butyl 2-hydroxyethyl(methyl)carbamate (1.23 g) obtained in Reference Synthetic Example 1 in tetrahydrofuran (15 mL) was added pyridine (0.68 mL), then a solution of 2-ethoxyethyl chlorocarbonate obtained above in tetrahydrofuran (5 mL) was added dropwise thereto, and stirred at room temperature for 3 days. The reaction solution was concentrated under reduced pressure, and water (50 mL) was added thereto, and then, extracted with ethyl acetate (50 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=1:5, then 2:3). The purified material was dissolved in diethyl ether (3 mL), and added 4N hydrogen chloride-ethyl acetate solution (3 mL). After stirring at room temperature overnight, the depositting solid was collected by filtration, and dried under reduced pressure to give title compound as white solid (0.94 g).

1. temperaturecooling
2. concentrationThe reaction solution was concentrated under reduced pressure
3. additionto the residue was added water (50 mL)
4. extractionextracted with ethyl acetate (50 mL)
5. washThe ethyl acetate layer was washed with 0.2 N hydrochloric acid (20 mL) and saturated brine (50 mL)
6. dry with materialdried over anhydrous magnesium sulfate
7. concentrationThe solution was concentrated under reduced pressure

ORD record

ord-bdef6084a0b64e00831f4d6f946a6359

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08449911B2