Piconol → 8-Hydroxy-2-methyl-4-(2-pyridylmethoxy)quinoline

HRID 850179Notes

Reaction equation

HRID 850179 reaction equation
[OH:1][CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][N:4]=1.[H-].[Na+].Cl[C:12]1[C:21]2[C:16](=[C:17]([OH:22])[CH:18]=[CH:19][CH:20]=2)[N:15]=[C:14]([CH3:23])[CH:13]=1>CC1(C)NC=NC1=O.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[OH:22][C:17]1[CH:18]=[CH:19][CH:20]=[C:21]2[C:16]=1[N:15]=[C:14]([CH3:23])[CH:13]=[C:12]2[O:1][CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][N:4]=1

Participants

6

Reactant 3

HCID 11474PiconolHCID 24758Sodium hydrideHCID 122197224-Chloro-8-hydroxy-2-methylquinoline

Product 1

HCID 110867028-Hydroxy-2-methyl-4-(2-pyridylmethoxy)quinolineYield 49.1%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 178430617HCID 178430617, compoundSolvent

Procedure

To an ice-cooled solution of 2-hydroxymethylpyridine (164 mg) in anhydrous dimethylimidazolinone (2 ml) was added sodium hydride (40% in oil, 100 mg), and the mixture was stirred at the same temperature for 30 minutes. To this mixture were added 4-chloro-8-hydroxy-2-methylquinoline (194 mg) and tetrabutylammonium iodide (185 mg). The mixture was stirred at 100° C. for 8 hours and partitioned between ethyl acetate and water. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with water three times, dried over magnesium sulfate and evaporated in vacuo. The residue was purified by a silica gel column chromatography (n-hexane-ethyl acetate) followed by trituration with n-hexane to give 8-hydroxy-2-methyl-4-(2-pyridylmethoxy)quinoline (131 mg) as a pale yellow powder.

Workup

  1. stirringThe mixture was stirred at 100° C. for 8 hours
  2. custompartitioned between ethyl acetate and water
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with ethyl acetate
  5. washwashed with water three times
  6. dry with materialdried over magnesium sulfate
  7. customevaporated in vacuo
  8. customThe residue was purified by a silica gel column chromatography (n-hexane-ethyl acetate)

Sources & evidence

ORD record
ord-c5fac3d5bbf7401b9e5a0e2307715645
Source dataset
uspto-grants-2000_01
Patent number
US06015818

Reaction notes

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