Iodoethane → 8-Ethoxy-2-methylquinoline

HRID 623389Notes

Reaction equation

HRID 623389 reaction equation
[CH2:1](I)[CH3:2].BrC(C)C.C[C:9]1([CH3:19])[CH:18]=[CH:17][C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[NH:10]1.C([O-])([O-])=[O:21].[K+].[K+]>CN(C=O)C>[CH2:1]([O:21][C:12]1[CH:13]=[CH:14][CH:15]=[C:16]2[C:11]=1[N:10]=[C:9]([CH3:19])[CH:18]=[CH:17]2)[CH3:2]

Participants

6

Reactant 4

HCID 6340IodoethaneHCID 63582-BromopropaneHCID 11430Potassium CarbonateHCID 124373012,2-Dimethyl-1,2-dihydroquinoline

Product 1

HCID 18454248-Ethoxy-2-methylquinoline

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Ethyl iodide (3.9 g, 25.0 mmol) or 2-bromopropane (2.4 g, 19.2 mmol) was added to a stirred solution of 2-methylquinaldine (3.0 g, 18.8 mmol) and K2CO3 (6.5 g 47 mmol; 5.2 g, 37.6 mmol) in 30 ml DMF at 60° C. for 14 h. The reaction mixture was quenched by H2O (200 ml) and extracted with EtOAc (50 ml×2). The organic layer was concentrated by evaporation in vacuum. The residue was purified by flash column chromatography with Hex/EA (6:1) and recrystallized with Hexane/EA to give 8-ethoxy-2-methylquinoline as intermediate (2.75 g, 78%) in solid but liquid form for 8-isopropopxy-2-methylquinoline (2.92 g, 77%). LHMDS (2.2 equiv.) was treated with a stirred solution of different intermediates in THF solution at 0° C. for 1 h. Corresponding Br(CH2)n−1OH (1.1-1.2 equiv.) was added to a reaction mixture and recover to RT for further 12 to 30 h. The solvent was removed under a reduced pressure. The brown oily residue was purified by flash column chromatography with Hex/EA or DCM/BA and recrystallized by Hexane/EA to afford compound D and E.

Workup

  1. customThe reaction mixture was quenched by H2O (200 ml)
  2. extractionextracted with EtOAc (50 ml×2)
  3. concentrationThe organic layer was concentrated by evaporation in vacuum
  4. customThe residue was purified by flash column chromatography with Hex/EA (6:1)
  5. customrecrystallized with Hexane/EA

Sources & evidence

ORD record
ord-d2f3bc539fd34be89cc87d04285e1a52
Source dataset
uspto-grants-2016_04
Patent number
US09302992B2

Reaction notes

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