Acetic Acid → HCID 20279349, compound

HRID 883646Notes

Reaction equation

HRID 883646 reaction equation
C[O:2][C:3](=O)[CH:4]([C:7]1([C:18]#[N:19])[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([Cl:16])[CH:14]=2)[NH:9][C:8]1=[O:17])C#N.Cl.C(O)(=[O:24])C>CO>[Cl:16][C:13]1[CH:14]=[C:15]2[C:7]3([CH2:4][C:3](=[O:2])[NH:19][C:18]3=[O:24])[C:8](=[O:17])[NH:9][C:10]2=[CH:11][CH:12]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 24829234(5-chloro-3-cyano-2-oxo-2,3-dihydro-1H-indol-3-yl)-cyanoacetic acid methyl ester

Product 1

HCID 20279349HCID 20279349, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A stirred solution of the crude (5-chloro-3-cyano-2-oxo-2,3-dihydro-1H-indol-3-yl)-cyanoacetic acid methyl ester, intermediate 5 (53.3 g, 0.18 mol) in methanol (450 ml) was cooled in an ice-water bath and saturated with hydrogen chloride gas, keeping the temperature below 20° C. The resultant solution was left to stand at ambient temperature overnight and then heated cautiously under reflux for 5 hours to give a yellow suspension. The solvent was removed in vacuo to give a semi-solid residue, which was mixed with glacial acetic acid (375 ml) and heated under reflux, with stirring, for 16 hours. After cooling in an ice-water bath, the crude 5-chloro-1H-spiro[indole-3,3′-pyrrolidine]-2,2′,5′-trione was removed by filtration, washed with cold glacial acetic acid (100 ml) followed by water (100 ml) and then diethyl ether (100 ml) and dried in vacuo to give an off-white solid. A second crop was obtained by removing the solvent in vacuo from the combined acetic acid filtrates and repeating the purification procedure to give a total of 30.5 g (66%). Sufficiently pure by 1H NMR for subsequent reaction.

Workup

  1. customthe temperature below 20° C
  2. temperatureheated cautiously
  3. temperatureunder reflux for 5 hours
  4. customto give a yellow suspension
  5. customThe solvent was removed in vacuo
  6. customto give a semi-solid residue, which
  7. temperatureheated
  8. temperatureunder reflux
  9. temperatureAfter cooling in an ice-water bath
  10. customthe crude 5-chloro-1H-spiro[indole-3,3′-pyrrolidine]-2,2′,5′-trione was removed by filtration
  11. washwashed with cold glacial acetic acid (100 ml)
  12. dry with materialdiethyl ether (100 ml) and dried in vacuo
  13. customto give an off-white solid
  14. customA second crop was obtained
  15. customby removing the solvent in vacuo from the combined acetic acid filtrates
  16. customthe purification procedure
  17. customto give a total of 30.5 g (66%)
  18. customSufficiently pure by 1H NMR for subsequent reaction

Sources & evidence

ORD record
ord-4bf9520c1d9144c2bd65f77087e4004f
Source dataset
uspto-grants-2012_08
Patent number
US08236963B2

Reaction notes

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