Reaction #73006

Reaction equation

p-toluenesulfonyl chloride

ammonium hydroxide

1-{3-[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]propyl}cyclohexanol

m-CPBA

→

1-{3-[4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]propyl}cyclohexanol

Yield 53.0%

Solvents

chloroform

Conditions

Workup

1. 1
   workup.STIRRINGThe mixture was stirred at 0° C. for 1 h
2. 2
   Filtrationwas filtered
3. 3
   workup.ADDITIONThe filtrate was diluted with dichloromethane (30 mL) and saturated aqueous sodium bicarbonate (30 mL)
4. 4
   OtherThe layers were separated
5. 5
   Extractionthe aqueous layer was extracted with dichloromethane (20 mL)
6. 6
   Dryingdried over MgSO4
7. 7
   Filtrationfiltered
8. 8
   Concentrationconcentrated
9. 9
   Otherto afford an orange solid, which
10. 10
    Otherwas purified by HPFC (silica gel, eluted with 0-35% CMA/chloroform)
11. 11
    ConcentrationThe appropriate fractions were concentrated
12. 12
    Otherto afford a tan solid
13. 13
    Otherthat was crystallized from chloroform/hexanes
14. 14
    Otherdried at 75° C. under vacuum

Procedure

To a solution of 1-{3-[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]propyl}cyclohexanol (1.10 g, 2.99 mmol) in chloroform (15 mL) at rt was added m-CPBA (0.96 g, 3.89 mmol) in portions. The reaction was stirred for 1.5 h, then was cooled to 0° C. and concentrated ammonium hydroxide (5 mL) was added followed by portionwise addition of p-toluenesulfonyl chloride (0.630 g, 3.29 mmol). The mixture was stirred at 0° C. for 1 h, then was filtered. The filtrate was diluted with dichloromethane (30 mL) and saturated aqueous sodium bicarbonate (30 mL). The layers were separated and the aqueous layer was extracted with dichloromethane (20 mL). The organic layers were combined, dried over MgSO4, filtered, and concentrated to afford an orange solid, which was purified by HPFC (silica gel, eluted with 0-35% CMA/chloroform). The appropriate fractions were concentrated to afford a tan solid that was crystallized from chloroform/hexanes and dried at 75° C. under vacuum to afford 1-{3-[4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]propyl}cyclohexanol as white crystals (600 mg, 53%), mp 175-176° C. Anal. calcd for C22H30N4O2: C, 69.08; H, 7.91; N, 14.65.

Source