Propargyl bromide → 3-(2-Methyl-1H-imidazo[4,5-c]quinolin-1-yl)propyl (Prop-2-ynyl) Ether

HRID 1839132ノート

反応式

HRID 1839132 の反応式
[CH3:1][C:2]1[N:3]([CH2:15][CH2:16][CH2:17][OH:18])[C:4]2[C:13]3[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=3[N:7]=[CH:6][C:5]=2[N:14]=1.[OH-].[Na+].[CH2:21](Br)[C:22]#[CH:23]>ClCCl.[Cl-].C([N+](C)(C)C)C1C=CC=CC=1>[CH2:23]([O:18][CH2:17][CH2:16][CH2:15][N:3]1[C:4]2[C:13]3[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=3[N:7]=[CH:6][C:5]=2[N:14]=[C:2]1[CH3:1])[C:22]#[CH:21]

参加物

6

反応物 3

HCID 7842Propargyl bromide2 回HCID 14798Sodium HydroxideHCID 222544433-(2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)-1-propanol

生成物 1

HCID 858834993-(2-Methyl-1H-imidazo[4,5-c]quinolin-1-yl)propyl (Prop-2-ynyl) Ether収率 33%

試薬・触媒・溶媒 2

HCID 5963Benzyltrimethylammonium chloride触媒HCID 6344Dichloromethane溶媒

実験手順

To 3-(2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)-1-propanol (12.2 g, 50.56 mmol) dissolved in dichloromethane (180 mL) was added sodium hydroxide (180 mL of 50%) with mechanical stirring. Benzyltrimethylammonium chloride (1.88 g, 10.11 mmol) was added to the resulting suspension, and after stirring for 5 minutes, propargyl bromide (17 mL of 80% in toluene, 141.8 mmol) was added. The resulting reaction mixture was allowed to stir at ambient temperature. After 2 hours, TLC monitoring indicated 50% completion, and after 4.5 hours HPLC monitoring indicated 20% starting material remaining. More propargyl bromide (5 mL of 80% in toluene, 40.51 mmol) was added, and the resulting reaction mixture was allowed to stir at ambient temperature for 64.5 hours. The layers were separated, and the organic layer was washed with water (3×) and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting dark oil was dissolved in dichloromethane and again extracted with water, dried over sodium sulfate, and concentrated under reduced pressure. The resulting dark oil was purified by silica gel column chromatography using 98/2 dichloromethane/methanol as the eluant. After removing the solvent from the collected fractions, 5.880 g of pure (by HNMR analysis) product was obtained. This material was recrystallized from ethyl acetate/hexane to provide 4.658 g of brown crystals.

後処理

  1. customThe resulting reaction mixture
  2. stirringto stir at ambient temperature
  3. waitAfter 2 hours
  4. waitafter 4.5 hours HPLC monitoring indicated
  5. customthe resulting reaction mixture
  6. stirringto stir at ambient temperature for 64.5 hours
  7. customThe layers were separated
  8. washthe organic layer was washed with water (3×) and brine
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. dissolutionThe resulting dark oil was dissolved in dichloromethane
  13. extractionagain extracted with water
  14. dry with materialdried over sodium sulfate
  15. concentrationconcentrated under reduced pressure
  16. customThe resulting dark oil was purified by silica gel column chromatography
  17. customAfter removing the solvent from the collected fractions, 5.880 g of pure (by HNMR analysis) product
  18. customwas obtained
  19. customThis material was recrystallized from ethyl acetate/hexane

出典と根拠

ORDレコード
ord-fbe05ef5856e45428c791fdad5867f67
出典データセット
uspto-grants-2004_01
特許番号
US06677348B2

反応ノート

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