Pyridine → HCID 23093485, compound

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).

1. additionwas added dropwise
2. stirringstirred for 1 hr
3. concentrationthe reaction solution was concentrated under reduced pressure
4. additionTo the residue was added water (50 mL)
5. extractionextracted with ethyl acetate (80 mL)
6. washThe ethyl acetate layer was washed with 5% aqueous solution of citric acid (50 mL) and saturated saline (50 mL)
7. dry with materialdried over anhydrous magnesium sulfate
8. concentrationby concentrating under reduced pressure
9. customThe residue was purified with silica gel column chromatography (
10. washeluted with ethyl acetate
11. dissolutionThe purified material (3.40 g) was dissolved in diethyl ether (5 mL)
12. additionadded 4N hydrogen chloride-ethyl acetate solution (5 mL)
13. stirringAfter stirring at room temperature overnight
14. concentrationthe reaction solution was concentrated under reduced pressure
15. additionBy adding diethyl ether
16. customto crystallize

ORD record

ord-3f2d23209a4841aca3699adc2c85138c

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08449911B2