Methanol → 2-Chloro-4-methoxy-6-methylquinoline

HRID 430086Notes

Reaction equation

HRID 430086 reaction equation
[Cl:1][C:2]1[CH:11]=[C:10](Cl)[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([CH3:13])[CH:8]=2)[N:3]=1.[OH-:14].[K+].[CH3:16]O>>[Cl:1][C:2]1[CH:11]=[C:10]([O:14][CH3:16])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([CH3:13])[CH:8]=2)[N:3]=1

Participants

4

Reactant 3

HCID 887MethanolHCID 14797Potassium HydroxideHCID 27546682,4-Dichloro-6-methylquinoline

Product 1

HCID 183537192-Chloro-4-methoxy-6-methylquinoline

Procedure

To 2,4-dichloro-6-methylquinoline (4.1 g, 19 mmol) in methanol (34 ml) was added KOH (1.42 g) and the resulting solution was heated under reflux for 2.5 h. The mixture was concentrated in vacuo and partitioned between ethyl acetate and half-concentrated brine. The organic layer was concentrated and chromatographed (silica gel, EtOAc:hexanes 1:5→1:3). 4-Chloro-2-methoxy-6-methylquinoline eluted first, then 2,4-dichloro-6-methylquinoline, followed by the colourless crystalline title compound, (1.97 g, 49%). δH (CDCl3) 2.52 (s, 3H), 4.05 (s, 3H), 6.71 (s, 1H), 7.53 (dd, J=8.6, 2.0, 1H), 7.83 (d, J=8.6, 1 H), 7.90 (br, s, 1 H); MS (AP+) 208 (MH+, 100%).

Workup

  1. temperaturethe resulting solution was heated
  2. temperatureunder reflux for 2.5 h
  3. concentrationThe mixture was concentrated in vacuo
  4. custompartitioned between ethyl acetate and half-concentrated brine
  5. concentrationThe organic layer was concentrated
  6. customchromatographed (silica gel, EtOAc:hexanes 1:5→1:3)
  7. wash4-Chloro-2-methoxy-6-methylquinoline eluted first

Sources & evidence

ORD record
ord-e9625519c4b2439a980f784e91b06e6a
Source dataset
uspto-grants-2001_11
Patent number
US06320051B1

Reaction notes

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