Hydrochloric Acid → 4-[(2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-yl)methyl]piperidin-4-ol

HRID 44731Notes

Reaction equation

HRID 44731 reaction equation
[CH2:1]([O:3][CH2:4][C:5]1[N:6]([CH2:18][C:19]2([OH:32])[CH2:24][CH2:23][N:22](C(OC(C)(C)C)=O)[CH2:21][CH2:20]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].Cl>C(O)C>[CH2:1]([O:3][CH2:4][C:5]1[N:6]([CH2:18][C:19]2([OH:32])[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]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]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 57515386tert-butyl 4-[(2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-yl)methyl]-4-hydroxypiperidine-1-carboxylate

Product 1

HCID 575154124-[(2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-yl)methyl]piperidin-4-olYield 61%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

To a solution of tert-butyl 4-{[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]methyl}-4-hydroxypiperidine-1-carboxylate (prepared as described in Part E of Example 4, 14.94 g, 33.91 mmol) in ethanol (170 mL) was added a solution of HCl in ethanol (2.7 M, 31 mL, 84.7 mmol). The solution was heated at reflux for 1 h, during which time a precipitate formed. The mixture was allowed to cool to rt and the volatiles were removed under reduced pressure. To the residue was added water (400 mL) followed by 50% aqueous NaOH until the pH=10. The solution was extracted with dichloromethane (3×100 mL). The aqueous layer was treated with 50% aqueous NaOH until the pH=12, then was extracted with dichloromethane (2×100 mL). The organic layers were combined, dried over Na2SO4, filtered, and concentrated under reduced pressure. The resulting solid was triturated with hot ethyl acetate and the remaining solid was isolated by filtration to afford 4-{[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]methyl}piperidin-4-ol (7.0 g, 61%) as an off-white powder.

Workup

  1. temperatureThe solution was heated
  2. temperatureat reflux for 1 h, during which time a precipitate
  3. customformed
  4. customthe volatiles were removed under reduced pressure
  5. additionTo the residue was added water (400 mL)
  6. extractionThe solution was extracted with dichloromethane (3×100 mL)
  7. additionThe aqueous layer was treated with 50% aqueous NaOH until the pH=12
  8. extractionwas extracted with dichloromethane (2×100 mL)
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe resulting solid was triturated with hot ethyl acetate
  13. customthe remaining solid was isolated by filtration

Sources & evidence

ORD record
ord-3863be8313c542508691bf3a20f8ec0e
Source dataset
uspto-grants-2013_09
Patent number
US08541438B2

Reaction notes

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