Methyl iodide → 8-Methoxy-2-Methylquinoline

HRID 623388Notes

Reaction equation

HRID 623388 reaction equation
CI.[CH3:3][C:4]1(C)[CH:13]=[CH:12][C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[NH:5]1.[C:15]([O-])([O-])=[O:16].[K+].[K+]>CC(C)=O>[CH3:15][O:16][C:7]1[CH:8]=[CH:9][CH:10]=[C:11]2[C:6]=1[N:5]=[C:4]([CH3:3])[CH:13]=[CH:12]2

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 124373012,2-Dimethyl-1,2-dihydroquinoline

Product 1

HCID 3169868-Methoxy-2-Methylquinoline

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

Methyl iodide (10.8 g, 76.3 mmol) was added to a stirred solution of 2-methylquinaldine (1.0 g, 6.3 mmol) and K2CO3 (5.0 g, 36.2 mmol) in 30 ml acetone at RT for 10 h. The reaction mixture was filtered and filtrate removed under a reduced pressure. The residue was purified by flash column chromatography with Hex/EA (3:1) and recrystallized with Hexane/EA to give 8-methoxy-2-methylquinoline as intermediates. LHMDS (2.2 to 2.5 equiv.) was treated with a stirred solution of intermediate (1 equiv.) in THF at 0° C. for 1 h. Corresponding Br(CH2)n−1OH (1.0 to 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/EA and recrystallized by Hex/EA to afford series of compounds C.

Workup

  1. filtrationThe reaction mixture was filtered
  2. customfiltrate removed under a reduced pressure
  3. customThe residue was purified by flash column chromatography with Hex/EA (3:1)
  4. customrecrystallized with Hexane/EA

Sources & evidence

ORD record
ord-e3940a4d8f204395935e9f6d51ef5934
Source dataset
uspto-grants-2016_04
Patent number
US09302992B2

Reaction notes

Loading…