Phenol → 6-(2-Quinolinylmethoxy)-2-methyl-1-indanone

HRID 37695Notes

Reaction equation

HRID 37695 reaction equation
[C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:8](=[O:11])([O-])[O-].[K+].[K+].C1OCCOCCOCCOCCOCCOC1.Cl[CH2:33][C:34]1[CH:43]=[CH:42][C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[N:35]=1.[CH3:44][CH2:45][CH2:46]CCC>ClCCl.CO.C(#N)C>[N:35]1[C:36]2[C:41](=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH:42]=[CH:43][C:34]=1[CH2:33][O:7][C:1]1[CH:6]=[C:5]2[C:4]([CH2:44][CH:45]([CH3:46])[C:8]2=[O:11])=[CH:3][CH:2]=1

Participants

8

Reactant 5

HCID 996PhenolHCID 8058HexaneHCID 11430Potassium CarbonateHCID 203942-(Chloromethyl)quinolineHCID 2855718-Crown-6

Product 1

HCID 199357276-(2-Quinolinylmethoxy)-2-methyl-1-indanoneYield 84.8%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

A mixture of the phenol (15. 1 6 g, 93.58 mmole) of Step D, powdered anhydrous potassium carbonate (12.93 g, 93.6 mmole), 18-crown-6 (2.47 g, 9.36 mmole) and dry acetonitrile (200 mL) is stirred at room temperature under a nitrogen for 15 minutes. 2-Chloromethylquinoline (free base, freshly prepared from 18.29 g or 102.96 mmole of the hydrochloride salt) is added in one portion and the mixture is placed in an oil bath heated at 65° C. for 11 hours (TLC, dichloromethane-methanol 9: 1, UV). The solvent is removed in vacuo and the residue is partitioned between ethyl acetate and water. The organic phase is washed with brine, dried (MgSO4) and evaporated to yield an oil which solidifies upon trituration with hexane (ca. 31 g). The crude product is purified by flash chromatography (on silica Merck-60, absorbed in methylene chloride, eluted with CH2Cl2 -ethyl acetate 90:10 and 85:15) to provide 5.95 g of slightly impure material together with 24.55 g of the pure title compound (pale yellow solid, 84.8%).

Workup

  1. additionis added in one portion
  2. customthe mixture is placed in an oil bath
  3. customThe solvent is removed in vacuo
  4. customthe residue is partitioned between ethyl acetate and water
  5. washThe organic phase is washed with brine
  6. dry with materialdried (MgSO4)
  7. customevaporated
  8. customto yield an oil which
  9. customThe crude product is purified by flash chromatography (on silica Merck-60, absorbed in methylene chloride, eluted with CH2Cl2 -ethyl acetate 90:10 and 85:15)

Sources & evidence

ORD record
ord-62663c77bbbf4ec6ab9e7fc418b43d17
Source dataset
uspto-grants-1995_05
Patent number
US05420289

Reaction notes

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