Sodium Bicarbonate → (11S)-11-isopropyl-10,11-dihydro-8H-[1,4]oxazino[4',3':1,2]imidazo[4,5-c]quinoline

온도

-78 °C

1-[(1S)-1-({[tert-Butyl(dimethyl)silyl]oxy}methyl)-2-methylpropyl]-2-(chloromethyl)-1H-imidazo[4,5-c]quinoline (4.85 g, 11.6 mmol) was dissolved in 110 mL of tetrahydrofuran (THF) and the solution was cooled to −78° C. under N2. A 1.0 M solution of tetrabutylammonium fluoride in THF (12.8 mL) was added and the reaction mixture was allowed to warm to 0° C. overnight. The reaction mixture was then treated with 50 mL of saturated sodium bicarbonate solution and 100 mL of CHCl3. The layers were separated and the organic portion was washed with H2O (50 mL) and brine (4×25 mL). The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure to give a yellow syrup. The syrup was concentrated from toluene (3×) to give a pale yellow foam. This material was dissolved in 100 mL of anhydrous THF and the solution was cooled 0° C. and stirred under N2. Solid potassium tert-butoxide was then added and the reaction mixture was allowed to warm to ambient overnight. The THF was then removed under reduced pressure and the resulting material was partitioned between 100 mL of CHCl3 and 100 mL of saturated sodium bicarbonate solution. The layers were separated and the organic portion was washed with H2O and brine. The organic portion was then dried over Na2SO4, filtered and concentrated under reduced to give brown foam. Chromatography (SiO2, 0%-50% 80:18:2 CHCl3/methanol/concentrated NH4OH(CMA) in CHCl3) gave (11S)-11-isopropyl-10,11-dihydro-8H-[1,4]oxazino[4′,3′:1,2]imidazo[4,5-c]quinoline (2.13 g) as a light yellow solid.

1. temperatureto warm to 0° C. overnight
2. customThe layers were separated
3. washthe organic portion was washed with H2O (50 mL) and brine (4×25 mL)
4. dry with materialThe organic layer was dried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customto give a yellow syrup
8. concentrationThe syrup was concentrated from toluene (3×)
9. customto give a pale yellow foam
10. temperaturethe solution was cooled 0° C.
11. temperatureto warm to ambient overnight
12. customThe THF was then removed under reduced pressure
13. customthe resulting material was partitioned between 100 mL of CHCl3 and 100 mL of saturated sodium bicarbonate solution
14. customThe layers were separated
15. washthe organic portion was washed with H2O and brine
16. dry with materialThe organic portion was then dried over Na2SO4
17. filtrationfiltered
18. concentrationconcentrated
19. customto give brown foam

ORD 기록

ord-058511b76fe949cb83ea92b530978eab

출처 데이터셋

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08546383B2