4-Toluenesulfonyl chloride → HCID 58837345, compound

To a stirred solution of ethyl 4-[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butanoate (15.4 g, 45.1 mmol) in dichloromethane (150 mL) at 0° C. was added mCPBA (approximately 77% purity, 19.7 g, 87.9 mmol) in portions. The reaction mixture was stirred at room temperature for 1.5 hours, then concentrated ammonium hydroxide (50 mL) was added. p-Toluenesulfonyl chloride was added in portions to the mixture, which was stirred for 1 hour then filtered. The filtrate was transferred to a separatory funnel, saturated aqueous sodium bicarbonate (50 mL) was added and the layers were separated. The aqueous layer was extracted with dichloromethane (2×50 mL). The organic layers were combined, washed with 5% aqueous sodium hydroxide (2×75 mL), dried over potassium carbonate, filtered, and concentrated under reduced pressure to yield a brown solid that was slurried in ethyl acetate (50 mL) and filtered. The filtrate was concentrated under reduced pressure and the solid was recrystallized from ethanol/water four times, then was dissolved in dichloromethane (100 mL). The solution was washed with saturated aqueous sodium bicarbonate (2×50 mL), then was concentrated under reduced pressure to yield a solid that was recrystallized from ethanol/water three times. The crystals were dried in a vacuum oven at 70° C. to provide ethyl 4-[4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butanoate as pale yellow crystals, mp 129-131° C.

1. stirringwas stirred for 1 hour
2. filtrationthen filtered
3. customThe filtrate was transferred to a separatory funnel
4. additionsaturated aqueous sodium bicarbonate (50 mL) was added
5. customthe layers were separated
6. extractionThe aqueous layer was extracted with dichloromethane (2×50 mL)
7. washwashed with 5% aqueous sodium hydroxide (2×75 mL)
8. dry with materialdried over potassium carbonate
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customto yield a brown solid that
12. filtrationfiltered
13. concentrationThe filtrate was concentrated under reduced pressure
14. customthe solid was recrystallized from ethanol/water four times
15. dissolutionwas dissolved in dichloromethane (100 mL)
16. washThe solution was washed with saturated aqueous sodium bicarbonate (2×50 mL)
17. concentrationwas concentrated under reduced pressure
18. customto yield a solid
19. customthat was recrystallized from ethanol/water three times
20. customThe crystals were dried in a vacuum oven at 70° C.

ORD record

ord-14d8dd11d21a4be4bcbf8f9649609949

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09328110B2