Cesium carbonate → tert-butyl[2-(2-ethoxymethyl-1-propyl-1H-imidazo[4,5-c]quinolin-8-yloxy)ethyl]carbamate

HRID 540813Notes

Reaction equation

HRID 540813 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:7]([O:9][CH2:10][C:11]1[N:12]([CH2:25][CH2:26][CH3:27])[C:13]2[C:22]3[CH:21]=[C:20]([OH:23])[CH:19]=[CH:18][C:17]=3[N:16]=[CH:15][C:14]=2[N:24]=1)[CH3:8].I[CH2:29][CH2:30][NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35]>CN(C=O)C>[C:34]([O:33][C:32](=[O:38])[NH:31][CH2:30][CH2:29][O:23][C:20]1[CH:19]=[CH:18][C:17]2[N:16]=[CH:15][C:14]3[N:24]=[C:11]([CH2:10][O:9][CH2:7][CH3:8])[N:12]([CH2:25][CH2:26][CH3:27])[C:13]=3[C:22]=2[CH:21]=1)([CH3:37])([CH3:36])[CH3:35]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 641024tert-butyl N-(2-iodoethyl)carbamateHCID 670510882-ethoxymethyl-1-propyl-1H-imidazo[4,5-c]quinolin-8-ol

Product 1

HCID 131731977tert-butyl[2-(2-ethoxymethyl-1-propyl-1H-imidazo[4,5-c]quinolin-8-yloxy)ethyl]carbamateYield 90.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

Solid cesium carbonate (18.33 g, 56.22 mmol) was added to a solution of 2-ethoxymethyl-1-propyl-1H-imidazo[4,5-c]quinolin-8-ol (10.7 g, 37.5 mmol), prepared in Parts A-I, in DMF (185 mL). tert-Butyl 2-iodoethylcarbamate (11.17 g, 41.2 mmol), prepared in Parts J and K, was added, and the reaction mixture was heated at 65° C. for 18 hours. The solvent was removed under reduced pressure, and the residue was partitioned between dichloromethane and water. The organic fraction was washed with water (4×100 mL) and brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure to provide a black oil. The oil was purified by column chromatography on silica gel (eluting with 98:2 dichloromethane:methanol) to yield 14.6 g of tert-butyl[2-(2-ethoxymethyl-1-propyl-1H-imidazo[4,5-c]quinolin-8-yloxy)ethyl]carbamate as a tan, waxy solid.

Workup

  1. additionwas added
  2. customThe solvent was removed under reduced pressure
  3. customthe residue was partitioned between dichloromethane and water
  4. washThe organic fraction was washed with water (4×100 mL) and brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto provide a black oil
  9. customThe oil was purified by column chromatography on silica gel (eluting with 98:2 dichloromethane:methanol)

Sources & evidence

ORD record
ord-b2720fc745144896a469033ba9873c21
Source dataset
uspto-grants-2014_10
Patent number
US08871782B2

Reaction notes

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