Pyridine → Oxan-4-yl carbonochloridate

To a solution of bis(trichloromethyl) carbonate (2.97 g) in tetrahydrofuran (40 mL) was added dropwise a solution of pyridine (2.43 mL) in tetrahydrofuran (10 mL) under ice-cooling. The solution was stirred for 10 minutes under ice-cooling, and a solution of tetrahydropyran-4-ol (1.91 g) in tetrahydrofuran (20 mL) was slowly added dropwise. After stirring at room temperature for 2 hrs, the solution was concentrated under reduced pressure, and to the residue were added ethyl acetate (50 mL) and water (50 mL). The ethyl acetate layer was separated, and washed with 0.2 N hydrochloric acid (20 mL), and saturated saline (50 m), followed by drying over anhydrous magnesium sulfate. The solution was concentrated under reduced pressure to give tetrahydropyran-4-yl chlorocarbonate (1.53 g). To a mixture of tert-butyl 2-hydroxyethyl(methyl)carbamate (1.40 g) obtained in Reference Synthetic Example 1 and tetrahydrofuran (20 mL) was added pyridine (0.78 mL), and a solution of tetrahydropyran-4-yl chlorocarbonate (1.53 g) obtained above in tetrahydrofuran (10 mL) was added dropwise thereto, followed by stirring at room temperature overnight. 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 extract was washed with 5% aqueous solution of citric acid (50 mL), and saturated saline (50 mL), and dried over anhydrous magnesium sulfate. The solution was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (elute with ethyl acetate hexane=4:1, then 3:2). The obtained colorless oil (2.03 g) was dissolved in diethyl ether (2 mL), and added 4N hydrogen chloride-ethyl acetate solution (5 mL). After stirring at room temperature for 30 minutes, diethyl ether (10 mL) was added, followed by stirring overnight. The depositting solid was collected by filtration, and dried under reduced pressure to give title compound as white solid (1.20 g).

1. temperaturecooling
2. temperaturecooling
3. stirringAfter stirring at room temperature for 2 hrs
4. concentrationthe solution was concentrated under reduced pressure
5. additionto the residue were added ethyl acetate (50 mL) and water (50 mL)
6. customThe ethyl acetate layer was separated
7. washwashed with 0.2 N hydrochloric acid (20 mL), and saturated saline (50 m)
8. dry with materialby drying over anhydrous magnesium sulfate
9. concentrationThe solution was concentrated under reduced pressure

ORD record

ord-c0990154868540fcbd840c1a14b52fa1

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08449911B2