Isatin → 7-(Thiophen-3-yl)indoline-2,3-dione

HRID 2375518Notes

Reaction equation

HRID 2375518 reaction equation
[NH:1]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:4](=[O:5])[C:2]1=[O:3].[S:12]1[CH:16]=[CH:15][C:14](B(O)O)=[CH:13]1.C(=O)(O)[O-].[Na+].IC1C=CC=C2C=1NC(=O)C2=O>O.ClCCl.C(OCC)(=O)C.COCCOC>[S:12]1[CH:16]=[CH:15][C:14]([C:10]2[CH:9]=[CH:8][CH:7]=[C:6]3[C:11]=2[NH:1][C:2](=[O:3])[C:4]3=[O:5])=[CH:13]1

Participants

9

Reactant 4

HCID 7054IsatinHCID 516892Sodium BicarbonateHCID 581760Thiophene-3-boronic acidHCID 40437057-Iodoisatin

Product 1

HCID 160999037-(Thiophen-3-yl)indoline-2,3-dione

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

This compound was prepared according to the procedure described by Lisowski et al. J. Org. Chem., 2000, 65, 4193. To a 1 L 3-necked round-bottomed flask fitted with a reflux condenser were added intermediate 6 (2.0 g, 7.3 mmol) and tetrakis[triphenylphosphine]palladium (0.424 g, 0.367 mmol), followed by 115 mL ethylene glycol dimethyl ether. The atmosphere in the reaction vessel was made inert by opening to vacuum, then to a positive pressure of nitrogen (3×). Next, 3-thiopheneboronic acid (Aldrich, 1.03 g, 8.06 mmol) and a solution of sodium bicarbonate (1.23 g, 14.7 mmol) in 115 mL water were added, and the evacuation/nitrogen procedure repeated one more time. The reaction mixture was then refluxed until t.l.c. (10% ethyl acetate in dichloromethane) showed complete disappearance of 7-iodoisatin, 6, (1-3 hours). After cooling to room temperature, the organic solvent was removed under reduced pressure. The residue was diluted with 1M aqueous hydrochloric acid and extracted into ethyl acetate (3×). The organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered, and evaporated under reduced pressure. The crude product was purified by flash chromatography over silica gel, eluting with 3% ethyl acetate in dichloromethane, to give 7-(thien-3-yl)isatin, Intermediate 8, as a bright red crystalline material (0.91 g, 54% yield): 1H NMR (400 MHz, DMSO-D6) δ 7.15 (t, 1H) 7.36 (dd, J=4.9, 1.4 Hz, 1H) 7.50 (dt, J=7.3, 1.0 Hz, 1H) 7.68 (d, J=1.5 Hz, 1H) 7.71 (m, 2H) 7.75 (dd, J=2.9, 1.4 Hz, 1H) 10.86 (s, 1H).

Workup

  1. customThis compound was prepared
  2. customTo a 1 L 3-necked round-bottomed flask fitted with a reflux condenser
  3. temperatureThe reaction mixture was then refluxed until t.l.c
  4. customthe organic solvent was removed under reduced pressure
  5. additionThe residue was diluted with 1M aqueous hydrochloric acid
  6. extractionextracted into ethyl acetate (3×)
  7. washThe organic layer was washed with brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. customevaporated under reduced pressure
  11. customThe crude product was purified by flash chromatography over silica gel
  12. washeluting with 3% ethyl acetate in dichloromethane

Sources & evidence

ORD record
ord-235fdbabe84f42a193a2a0d223ef07be
Source dataset
uspto-grants-2008_12
Patent number
US07465799B2

Reaction notes

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