2-Chloroethyl methyl ether → 3-Isobutyryl-4-(2-methylphenylamino)-8-(2-methoxyethoxy)quinoline

HRID 1534497Notes

Reaction equation

HRID 1534497 reaction equation
[C:1]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([C:15]=1[NH:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[CH3:23])=[CH:13][CH:12]=[CH:11][C:10]=2[OH:24])(=[O:5])[CH:2]([CH3:4])[CH3:3].CC(C)([O-])C.[K+].[CH3:31][O:32][CH2:33][CH2:34]Cl>O1CCCC1>[C:1]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([C:15]=1[NH:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[CH3:23])=[CH:13][CH:12]=[CH:11][C:10]=2[O:24][CH2:34][CH2:33][O:32][CH3:31])(=[O:5])[CH:2]([CH3:4])[CH3:3]

Participants

5

Reactant 3

HCID 123162-Chloroethyl methyl etherHCID 103586453-Isobutyryl-4-(2-methylphenylamino) 8-hydroxyquinolineHCID 23665647Potassium tert-butoxide

Product 1

HCID 100910673-Isobutyryl-4-(2-methylphenylamino)-8-(2-methoxyethoxy)quinolineYield 11.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 3-isobutyryl-4-(2-methylphenylamino) 8-hydroxyquinoline (5.0 g, 15.6 mmol), potassium t-butoxide (2.63 g, 23.4 mmol) and 2-chloroethyl methyl ether (2.85 ml, 31.2 mmol) in tetrahydrofuran (250 ml) was heated at reflux for 3 days, then the solvent evaporated. Water was added, the product extracted into dichloromethane, and the organic extracts dried and evaporated. Chromatography (silica gel, ethyl acetate/2% acetic acid/0%-5% methanol) removed unchanged starting material, then further chromatography (silica gel, 1%-1.5% methanol in dichloromethane) and crystallization from petroleum ether (40-60) gave 3-isobutyryl-4-(2-methylphenylamino)-8-(2-methoxyethoxy)quinoline (0.67 g), m.p. 68°-70°.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 3 days
  3. customthe solvent evaporated
  4. additionWater was added
  5. extractionthe product extracted into dichloromethane
  6. customthe organic extracts dried
  7. customevaporated
  8. customChromatography (silica gel, ethyl acetate/2% acetic acid/0%-5% methanol) removed unchanged
  9. customfurther chromatography (silica gel, 1%-1.5% methanol in dichloromethane) and crystallization from petroleum ether (40-60)

Sources & evidence

ORD record
ord-fad5207901d443fdb9e624463a1aa38d
Source dataset
uspto-grants-1992_02
Patent number
US05089504

Reaction notes

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