Triethylamine → 8-{[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]methyl}-1,4-dioxaspiro[4,5]decan-8-ol

HRID 44714Notes

Reaction equation

HRID 44714 reaction equation
[CH2:1]([O:3][CH2:4][C:5](Cl)=O)[CH3:2].[NH2:8][C:9]1[CH:10]=[N:11][C:12]2[C:17]([C:18]=1[NH:19][CH2:20][C:21]1([OH:31])[CH2:30][CH2:29][C:24]3([O:28][CH2:27][CH2:26][O:25]3)[CH2:23][CH2:22]1)=[CH:16][CH:15]=[CH:14][CH:13]=2.C(N(CC)CC)C>ClCCl.C(O)C>[CH2:1]([O:3][CH2:4][C:5]1[N:19]([CH2:20][C:21]2([OH:31])[CH2:30][CH2:29][C:24]3([O:28][CH2:27][CH2:26][O:25]3)[CH2:23][CH2:22]2)[C:18]2[C:17]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[N:11]=[CH:10][C:9]=2[N:8]=1)[CH3:2]

Participants

6

Reactant 3

HCID 8471Triethylamine2×HCID 84189Ethoxyacetyl chloride2×HCID 669191388-{[(3-Aminoquinolin-4-yl)amino]methyl}-1,4-dioxaspiro[4,5]decan-8-ol

Product 1

HCID 669191728-{[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]methyl}-1,4-dioxaspiro[4,5]decan-8-olYield 19.4%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

A solution of ethoxyacetyl chloride (4.38 g, 35.7 mmol) in dichloromethane (50 mL) was added to a 0° C. solution of 8-{[(3-aminoquinolin-4-yl)amino]methyl}-1,4-dioxaspiro[4.5]decan-8-ol (10.7 g, 32.5 mmol) and triethylamine (4.98 mL, 35.7 mmol) in dichloromethane (250 mL). After one hour, the solution was allowed to warm to rt and stir for 2 d. More ethoxyacetyl chloride (0.15 equivalent) was added. After two hours, the solution was transferred to a separatory funnel and washed with water (200 mL). The organic layer was dried with Na2SO4, filtered, and concentrated under reduced pressure to yield an orange solid. The solid was dissolved in ethanol (150 mL) and triethylamine (13.6 mL, 97.4 mmol) was added. The solution was heated at reflux for 16 h. The volatiles were removed under reduced pressure to yield a brown oil that was crystallized from isopropanol to yield 8-{[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]methyl}-1,4-dioxaspiro[4.5]decan-8-ol as off-white crystals (2.50 g) and a second crop (1.50 g) of crystals. A third crop (4.91 g) was isolated after recrystallization of the mother liquor from ethyl acetate. A total of 8.91 g (69%) of 8-{[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]methyl}-1,4-dioxaspiro[4.5]decan-8-ol was isolated.

Workup

  1. waitAfter two hours
  2. customthe solution was transferred to a separatory funnel
  3. washwashed with water (200 mL)
  4. dry with materialThe organic layer was dried with Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto yield an orange solid
  8. temperatureThe solution was heated
  9. temperatureat reflux for 16 h
  10. customThe volatiles were removed under reduced pressure
  11. customto yield a brown oil that
  12. customwas crystallized from isopropanol

Sources & evidence

ORD record
ord-fc46cd9b20c64c7aa43c188ace7feba9
Source dataset
uspto-grants-2013_09
Patent number
US08541438B2

Reaction notes

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