Tetrahydrofuran → HCID 68006325, compound

A mixture of the compound of Reference Example 2 (4.05 g, 19.5 mmol), ethyl (chloroformyl)acetate (3.71 mL, 29.3 mmol), triethylamine (5.40 mL, 39.0 mmol) and THF (41 mL) was stirred at room temperature for 4 hr. To the reaction mixture was added saturated aqueous sodium hydrogen carbonate solution (100 mL), and the mixture was extracted with ethyl acetate (200 mL). The extract was washed with brine (100 mL), and dried over anhydrous sodium sulfate. The insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure. To the residue were added ethanol (188 ml) and 20% ethanol solution (13.3 mL, 39.0 mmol) of sodium ethoxide, and the mixture was stirred at 50° C. for 3 hr. The reaction mixture was concentrated under reduced pressure, and to the residue was added 1N hydrochloric acid (100 mL), and the mixture was extracted with ethyl acetate (200 mL). The extract was washed with brine (100 and dried over anhydrous sodium sulfate. The insoluble material was removed by filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluate, hexane:ethyl acetate=98:2→70:30) to give the title compound (3.15 g, 56%) as a yellow oil.

1. extractionthe mixture was extracted with ethyl acetate (200 mL)
2. washThe extract was washed with brine (100 mL)
3. dry with materialdried over anhydrous sodium sulfate
4. customThe insoluble material was removed by filtration
5. concentrationthe filtrate was concentrated under reduced pressure
6. stirringthe mixture was stirred at 50° C. for 3 hr
7. concentrationThe reaction mixture was concentrated under reduced pressure
8. additionto the residue was added 1N hydrochloric acid (100 mL)
9. extractionthe mixture was extracted with ethyl acetate (200 mL)
10. washThe extract was washed with brine (100
11. dry with materialdried over anhydrous sodium sulfate
12. customThe insoluble material was removed by filtration
13. concentrationthe filtrate was concentrated under reduced pressure
14. customthe residue was purified by silica gel column chromatography (eluate, hexane:ethyl acetate=98:2→70:30)

ORD record

ord-d0ab9910ed664098ad36cbdb4d3ba7f5

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08907089B2