Sodium Bicarbonate → HCID 86619530, compound

Temperature

-78 °C

tert-Butyl (2S)-3-{[tert-butyl(dimethyl)silyl]oxy}-2-[2-(chloromethyl)-1H-imidazo[4,5-c]quinolin-1-yl]propylcarbamate (3.11 g, 6.16 mmol) was dissolved in 60 mL of tetrahydrofuran (THF) and the solution was cooled to −78° C. under N2. A 1.0 M solution of tetrabutylammonium fluoride in THF (6.8 mL) was added and the reaction mixture was allowed to warm to −10° C. over 2 hours. The reaction mixture was then treated with 50 mL of saturated sodium bicarbonate solution and 200 mL of CH2Cl2. 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 golden syrup. The syrup was concentrated from toluene (3×) to give a pale yellow foam. This material was dissolved in 70 mL of anhydrous THF and the solution was stirred under N2. Solid potassium tert-butoxide (507 mg, 6.18 mmol) was then added and the reaction mixture was allowed to stir for 2.5 hours. A solution of 50 mL of saturated sodium bicarbonate was then added and the THF was then removed under reduced pressure. The resulting material was treated with 150 mL of CH2Cl2 and layers were separated. 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, 20% 80:18:2 CHCl3/methanol/concentrated NH4OH(CMA)/CHCl3) gave tert-butyl (11S)-10,11-dihydro-8H-[1,4]oxazino[4′,3′:1,2]imidazo[4,5-c]quinolin-11-ylmethylcarbamate (1.62 g) as a light yellow foam.

1. temperatureto warm to −10° C. over 2 hours
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 golden syrup
8. concentrationThe syrup was concentrated from toluene (3×)
9. customto give a pale yellow foam
10. stirringto stir for 2.5 hours
11. customthe THF was then removed under reduced pressure
12. additionThe resulting material was treated with 150 mL of CH2Cl2 and layers
13. customwere separated
14. washThe organic portion was washed with H2O and brine
15. dry with materialThe organic portion was then dried over Na2SO4
16. filtrationfiltered
17. concentrationconcentrated
18. customto give brown foam

ORD record

ord-942c9e4a91f64e869a08524eade900bf

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08350034B2