Epichlorohydrin → 2-[4-(2,3-epoxypropoxy)phenyl]-9-fluoro-4,4a,5,6-tetrahydrobenzo[h]cinnolin-3(2H)-one

HRID 727784Notes

Reaction equation

HRID 727784 reaction equation
[F:1][C:2]1[CH:23]=[CH:22][C:5]2[CH2:6][CH2:7][CH:8]3[C:13]([C:4]=2[CH:3]=1)=[N:12][N:11]([C:14]1[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=1)[C:10](=[O:21])[CH2:9]3.[OH-].[Na+].[CH2:26]([CH:28]1[O:30][CH2:29]1)Cl.C(OC(C)C)(C)C>CO>[O:30]1[CH2:29][CH:28]1[CH2:26][O:20][C:17]1[CH:18]=[CH:19][C:14]([N:11]2[C:10](=[O:21])[CH2:9][CH:8]3[C:13]([C:4]4[CH:3]=[C:2]([F:1])[CH:23]=[CH:22][C:5]=4[CH2:6][CH2:7]3)=[N:12]2)=[CH:15][CH:16]=1

Participants

6

Reactant 4

HCID 7835EpichlorohydrinHCID 7914Diisopropyl EtherHCID 14798Sodium HydroxideHCID 149869819-fluoro-2-(4-hydroxyphenyl)-4,4a,5,6-tetrahydrobenzo[h]cinnolin-3(2H)-one

Product 1

HCID 149869802-[4-(2,3-epoxypropoxy)phenyl]-9-fluoro-4,4a,5,6-tetrahydrobenzo[h]cinnolin-3(2H)-oneYield 37.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

To 50 ml of methanol is added 9 g of 9-fluoro-2-(4-hydroxyphenyl)-4,4a,5,6-tetrahydrobenzo[h]cinnolin-3(2H)-one, and 1.7 g of sodium hydroxide dissolved in 70 ml of methanol is added to the mixture under stirring at room temperature. Thereto is added 13 g of epichlorohydrin, and the mixture is heated under reflux for 2 hours. After the reaction mixture is filtered, the filtrate is concentrated under reduced pressure and the residue is extracted with chloroform. The extract is washed with water and dried over anhydrous magnesium sulfate. Thereafter, the solvent is distilled off to give 12.5 g of a brown oily substance. This oily substance is subjected to column chromatography. Isopropyl ether is added to the resulting crystals, and the crystals are collected by filtration to give 4 g of 2-[4-(2,3-epoxypropoxy)phenyl]-9-fluoro-4,4a,5,6-tetrahydrobenzo[h]cinnolin-3(2H)-one as white crystals, m.p. 128°-130° C.

Workup

  1. additionis added to the mixture
  2. temperaturethe mixture is heated
  3. temperatureunder reflux for 2 hours
  4. filtrationAfter the reaction mixture is filtered
  5. concentrationthe filtrate is concentrated under reduced pressure
  6. extractionthe residue is extracted with chloroform
  7. washThe extract is washed with water
  8. dry with materialdried over anhydrous magnesium sulfate
  9. distillationThereafter, the solvent is distilled off
  10. customto give 12.5 g of a brown oily substance
  11. filtrationthe crystals are collected by filtration

Sources & evidence

ORD record
ord-f951bcf02ff6484aaa1ab2fcd563baab
Source dataset
uspto-grants-1991_09
Patent number
US05045541

Reaction notes

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