Phosphorus oxychloride → 1-(2-Methyl-4-benzyloxyphenyl)-4-[(2-hydroxyethyl)amino]-6-beta,beta,beta-trifluoroethoxy-2,3-dihydropyrrolo[3,2-c]quinoline

HRID 849217Notes

Reaction equation

HRID 849217 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:5]=[CH:4][C:3]=1[N:16]1[C:28]2[C:27]3[CH:26]=[CH:25][CH:24]=[C:23]([O:29][CH2:30][C:31]([F:34])([F:33])[F:32])[C:22]=3[NH:21][C:20](=O)[C:19]=2[CH2:18][CH2:17]1.P(Cl)(Cl)(Cl)=O>>[CH3:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:5]=[CH:4][C:3]=1[N:16]1[C:28]2[C:27]3[CH:26]=[CH:25][CH:24]=[C:23]([O:29][CH2:30][C:31]([F:32])([F:33])[F:34])[C:22]=3[N:21]=[C:20]([NH:21][CH2:22][CH2:23][OH:29])[C:19]=2[CH2:18][CH2:17]1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 193697611-(2-Methyl-4-benzyloxyphenyl)-4-oxo-6-beta,beta,beta-trifluoroethoxy-2,3,4,5-tetrahydropyrrolo[3,2-c]quinoline

Product 1

HCID 193698341-(2-Methyl-4-benzyloxyphenyl)-4-[(2-hydroxyethyl)amino]-6-beta,beta,beta-trifluoroethoxy-2,3-dihydropyrrolo[3,2-c]quinolineYield 116%

Conditions

Temperature
110 °C

Procedure

1-(2-Methyl-4-benzyloxyphenyl)-4-oxo-6-β,β,β-trifluoroethoxy-2,3,4,5-tetrahydropyrrolo[3,2-c]quinoline(2.7 g, 5.6 mmol) was mixed with phosphoryl chloride(15 ml), and stirred at 110° C. for 30 minutes. After removing the excess phosphoryl chloride by distillation, the residue was dissolved in dichloromethane (50 ml), neutralized with aqueous solution of sodium bicarbonate, and stirred at room temperature for 30 minutes. The reaction mixture was extracted with dichloromethane, and the organic layer was washed with water for 3 times. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography(ethyl acetate:hexane=1:10) to obtain 1.7 g of desired compound as solid in 60% of yield.

Workup

  1. customAfter removing the excess phosphoryl chloride
  2. distillationby distillation
  3. dissolutionthe residue was dissolved in dichloromethane (50 ml)
  4. stirringstirred at room temperature for 30 minutes
  5. extractionThe reaction mixture was extracted with dichloromethane
  6. washthe organic layer was washed with water for 3 times
  7. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by silica gel column chromatography(ethyl acetate:hexane=1:10)

Sources & evidence

ORD record
ord-06edcc5da3f54e1a9c9859d4ac184fac
Source dataset
uspto-grants-2000_01
Patent number
US06011044

Reaction notes

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