Ethylene Glycol → 5'-Bromo-7'-methoxyspiro[[1,3]dioxolane-2,3'-indolin]-2'-one

HRID 1052982Notes

Reaction equation

HRID 1052982 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([O:11][CH3:12])[CH:10]=1)[NH:7][C:6](=[O:13])[C:5]2=[O:14].CC1C=CC(S(O)(=O)=O)=CC=1.[CH2:26](O)[CH2:27][OH:28]>C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([O:11][CH3:12])[CH:10]=1)[NH:7][C:6](=[O:13])[C:5]12[O:28][CH2:27][CH2:26][O:14]1

Participants

5

Reactant 3

HCID 174Ethylene GlycolHCID 6101p-Toluenesulfonic acidHCID 1176679885-bromo-7-methoxy-2,3-dihydro-1H-indole-2,3-dione

Product 1

HCID 1176738065'-Bromo-7'-methoxyspiro[[1,3]dioxolane-2,3'-indolin]-2'-oneYield 5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A stirred mixture of 5-bromo-7-methoxyindoline-2,3-dione (3.6 g, 14 mmol), p-TSA (1.14 g, 6 mmol) and toluene (100 mL) was refluxed using a Dean-Stark apparatus for 0.2 h. Ethylene glycol (9.3 g, 150 mmol, 10.7 eq.) was added and refluxed using a Dean-Stark apparatus for another 2 hours. The mixture was cooled and concentrated to 20 mL. EtOAc (100 mL) was added, washed with water (20 mL), brine (50 mL×2), dried over Na2SO4, filtered and concentrated under reduced pressure. Purified by column (CH2CL2/EtOAc=8:1) to give the desired product as a light brown solid (0.21 g, crude, 5%). 1H NMR (400 MHz, DMSO-d6): δH 10.66 (s, 1H), 7.48 (s, 1H), 7.26-7.27 (m, 1H), 7.13-7.14 (m, 1H), 4.25-4.31 (m, 4H), 3.86 (s, 3H). MS (ESI) m/e [M+1]+ 300/302.

Workup

  1. temperaturewas refluxed
  2. customfor 0.2 h
  3. temperaturerefluxed
  4. customfor another 2 hours
  5. temperatureThe mixture was cooled
  6. concentrationconcentrated to 20 mL
  7. additionEtOAc (100 mL) was added
  8. washwashed with water (20 mL), brine (50 mL×2)
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customPurified by column (CH2CL2/EtOAc=8:1)

Sources & evidence

ORD record
ord-63eceb57b5a646a1b91d20b80c3c78d3
Source dataset
uspto-grants-2016_07
Patent number
US09393232B2

Reaction notes

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