Pyridine → HCID 23093485, compound

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

1. additionwas dropwise added
2. stirringthe mixture was further stirred for 1 hr
3. concentrationThe reaction mixture was concentrated under reduced pressure and water (50 mL)
4. additionwas added to the residue
5. extractionThe mixture was extracted with ethyl acetate (80 mL)
6. washthe ethyl acetate layer was washed with a 5% aqueous citric acid solution (50 mL) and saturated brine (50 mL)
7. dry with materialdried over anhydrous magnesium sulfate
8. concentrationconcentrated under reduced pressure
9. customThe residue was purified by silica gel column chromatography (
10. washeluted with ethyl acetate
11. dissolutionThe purified product (3.40 g) was dissolved in diethyl ether (5 mL)
12. additiona 4N hydrogen chloride—ethyl acetate solution (5 mL) was added
13. stirringThe mixture was stirred overnight at room temperature
14. concentrationthe reaction mixture was concentrated under reduced pressure
15. additionDiethyl ether was added for crystallization

ORD record

ord-b0b8afdab90b44199702376153571d3f

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08980322B2