Diethylamine → 3-[5-(3-Diethylamino-propyl)-3,3-dimethyl-3H-isobenzofuran-1-ylidene]-5-fluoro-1,3-dihydro-indol-2-one

HRID 1254938Notes

Reaction equation

HRID 1254938 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]2=[C:12]1[C:20]2[C:15](=[CH:16][C:17]([CH2:21][CH2:22][CH2:23]OS(C)(=O)=O)=[CH:18][CH:19]=2)[C:14]([CH3:30])([CH3:29])[O:13]1.[CH2:31]([NH:33][CH2:34][CH3:35])[CH3:32]>O1CCOCC1.CCOC(C)=O>[CH2:31]([N:33]([CH2:34][CH3:35])[CH2:23][CH2:22][CH2:21][C:17]1[CH:16]=[C:15]2[C:20](=[CH:19][CH:18]=1)[C:12](=[C:5]1[C:4]3[C:8](=[CH:9][CH:10]=[C:2]([F:1])[CH:3]=3)[NH:7][C:6]1=[O:11])[O:13][C:14]2([CH3:29])[CH3:30])[CH3:32]

Participants

5

Reactant 2

HCID 8021DiethylamineHCID 76823955Methanesulfonic acid 3-[1-(5-fluoro-2-oxo-1,2-dihydro-indol-3-ylidene)-3,3-dimethyl-1,3-dihydro-isobenzofuran-5-yl]-propyl ester

Product 1

HCID 687174703-[5-(3-Diethylamino-propyl)-3,3-dimethyl-3H-isobenzofuran-1-ylidene]-5-fluoro-1,3-dihydro-indol-2-oneYield 55.2%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of methanesulfonic acid 3-[1-(5-fluoro-2-oxo-1,2-dihydro-indol-3-ylidene)-3,3-dimethyl-1,3-dihydro-isobenzofuran-5-yl]-propyl ester (170 mg, 0.39 mmol) and diethylamine (0.30 ml, 2.92 mmol) in dioxane (1.6 ml) was heated at 75° C. in a pressure tube for 36 hours. The mixture was evaporated, dissolved in EtOAc, and the EtOAc washed with H2O and brine. The aqueous layer was also extracted with CHCl3. The organic layers were combined, dried over anhydrous Na2SO4, and then evaporated to a yellow film. The sample was passed through a plug of silica gel eluting with 10% methanol in CHCl3 to give a yellow-orange solid. The solid was dissolved in EtOAc, washed with saturated aqueous NaHCO3, brine, dried over anhydrous Na2SO4, and evaporated to a yellow solid. The solid was chromatographed eluting with CHCl3/MeOH to give the title compound as a yellow solid (88 mg, 54%).

Workup

  1. customThe mixture was evaporated
  2. dissolutiondissolved in EtOAc
  3. washthe EtOAc washed with H2O and brine
  4. extractionThe aqueous layer was also extracted with CHCl3
  5. dry with materialdried over anhydrous Na2SO4
  6. customevaporated to a yellow film
  7. customto give a yellow-orange solid
  8. washwashed with saturated aqueous NaHCO3, brine
  9. dry with materialdried over anhydrous Na2SO4
  10. customevaporated to a yellow solid
  11. customThe solid was chromatographed
  12. washeluting with CHCl3/MeOH

Sources & evidence

ORD record
ord-8fda932bfecf488098ccde1f8a2bfc1b
Source dataset
uspto-grants-2013_06
Patent number
US08455656B2

Reaction notes

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