4-Toluenesulfonyl chloride → HCID 57515399, compound

HRID 44728Notes

Reaction equation

HRID 44728 reaction equation
[CH2:1]([O:3][CH2:4][C:5]1[N:6]([CH2:18][CH2:19][CH2:20][C:21]2([OH:27])[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]2)[C:7]2[C:16]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[N:10]=[CH:9][C:8]=2[N:17]=1)[CH3:2].C1C=C(Cl)C=C(C(OO)=O)C=1.[OH-].[NH4+:40].C1(C)C=CC(S(Cl)(=O)=O)=CC=1>C(Cl)(Cl)Cl>[NH2:40][C:9]1[C:8]2[N:17]=[C:5]([CH2:4][O:3][CH2:1][CH3:2])[N:6]([CH2:18][CH2:19][CH2:20][C:21]3([OH:27])[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26]3)[C:7]=2[C:16]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[N:10]=1

Participants

6

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 14923Ammonium HydroxideHCID 70297m-Chloroperbenzoic acidHCID 57515405HCID 57515405, compound

Product 1

HCID 57515399HCID 57515399, compoundYield 53%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
0 °C

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.

Workup

  1. stirringThe mixture was stirred at 0° C. for 1 h
  2. filtrationwas filtered
  3. additionThe filtrate was diluted with dichloromethane (30 mL) and saturated aqueous sodium bicarbonate (30 mL)
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with dichloromethane (20 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto afford an orange solid, which
  10. customwas purified by HPFC (silica gel, eluted with 0-35% CMA/chloroform)
  11. concentrationThe appropriate fractions were concentrated
  12. customto afford a tan solid
  13. customthat was crystallized from chloroform/hexanes
  14. customdried at 75° C. under vacuum

Sources & evidence

ORD record
ord-77255f4ca55f4ad7999bf385ff898983
Source dataset
uspto-grants-2013_09
Patent number
US08541438B2

Reaction notes

Loading…