Chloroform → HCID 67156889, compound

Temperature

50 °C

4-{[(11S)-5-Oxido-10,11-dihydro-8H-[1,4]oxazino[4′,3′:1,2]imidazo[4,5-c]quinolin-11-yl]methyl}phenyl acetate (3.08 g, 7.91 mmol) was dissolved in 100 mL of CH2Cl2 and treated with 10 mL of concentrated ammonium hydroxide solution. The mixture was stirred rapidly and then p-toluenesulfonyl chloride (1.51 g, 7.91 mmol) was carefully added. Rapid stirring continued for 1 hour. The reaction mixture was then treated with 20 mL of H2O and the layers were separated. The aqueous portion was extracted with CH2Cl2 (5×25 mL). The combined organic layers were washed with saturated NaHCO3 solution. Methanol was added to the organic layer to aid in solubility. The organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure to give a brown solid. Chromatography (SiO2, 20-40% CMA/CHCl3) gave a yellow solid. This material was dissolved in 100 mL 6 N aqueous HCl, and the solution was heated at 50° C. overnight. The reaction mixture was cooled and treated with concentrated ammonium hydroxide until pH=11 and then diluted with 200 mL H2O. The solution was extracted with 9:1 mixture of CH2Cl2/methanol (3×150 mL). The combined organic layers were washed sequentially with H2O and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure to give a white solid. Crystallization from ethanol containing HCl gave 4-{[(11S)-6-amino-10,11-dihydro-8H-[1,4]oxazino[4′,3′:1,2]imidazo[4,5-c]quinolin-11-yl]methyl}phenol hydrochloride (0.47 g) as an off white solid, mp>240° C. (dec).

1. stirringRapid stirring
2. customthe layers were separated
3. extractionThe aqueous portion was extracted with CH2Cl2 (5×25 mL)
4. washThe combined organic layers were washed with saturated NaHCO3 solution
5. additionMethanol was added to the organic layer
6. dry with materialThe organic layer was dried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customto give a brown solid
10. temperatureThe reaction mixture was cooled
11. extractionThe solution was extracted with 9:1 mixture of CH2Cl2/methanol (3×150 mL)
12. washThe combined organic layers were washed sequentially with H2O and brine
13. dry with materialdried over Na2SO4
14. filtrationfiltered
15. concentrationconcentrated under reduced pressure
16. customto give a white solid
17. customCrystallization from ethanol
18. additioncontaining HCl

ORD record

ord-d578b576730744e3b6a36fb799e493e9

Source dataset

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08207162B2