Hydrochloric Acid → HCID 20279332, compound

HRID 1632999Notes

Reaction equation

HRID 1632999 reaction equation
[C-:1]#[N:2].[K+].[Br:4][C:5]1[CH:29]=[CH:28][C:8]([CH2:9][N:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C-:12]([CH:19]([C:25]#[N:26])[C:20](OCC)=[O:21])[C:11]2=[O:27])=[C:7]([F:30])[CH:6]=1.Cl.C[OH:33]>C(OCC)(=O)C>[Br:4][C:5]1[CH:29]=[CH:28][C:8]([CH2:9][N:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12]3([CH:19]([C:25]#[N:26])[C:20](=[O:21])[NH:2][C:1]3=[O:33])[C:11]2=[O:27])=[C:7]([F:30])[CH:6]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 9032Potassium CyanideHCID 178471967HCID 178471967, compound

Product 1

HCID 20279332HCID 20279332, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Potassium cyanide (5.85 g.) was added to a solution of ethyl 2-[1-(4-bromo 2-fluorobenzyl)-2-oxo3-indolinidyl]-2-cyanoacetate (D) (35.0 g.) in methanol (80 ml.). The mixture was stirred for 2 hours, cooled to 0° C. and then saturated with dry hydrogen chloride at 0°-1O° C. The solution obtained was left overnight at ambient temperature, heated at 50°-55° C. for 1 hour and then under reflux for 4 hours. The cooled reaction solution deposited a solid which was collected; washed with water, air dried and then heated under reflux in acetic acid (85 ml.) for 12 hours. This mixture was cooled and the solid residue removed by filtration. The filtrate was evaporated, residual acetic acid being removed by azeotropic evaporation with toluene (3×150 ml.). The oily residue obtained was dissolved in ethyl acetate (100 ml.) and absorbed onto chromatographic silica gel (30 g.) by evaporation of the solvent. The residue was added to a column of silica gel (300 g.) made up in toluene. Elution with an increasing concentration of ethyl acetate in toluene (up to 25% v/v) and combination and evaporation of those fractions containing the major component (relative flow value 0.6), gave 1'-(4-bromo-2-flurobenzyl)-4-cyano-spiro[pyrrolidine3,3'-indoline]-2,2',5-trione (5.5 g.), m.p. 208°-210° C., after recrystallisation from ethyl acetate/petrol 60-80.

Workup

  1. customat 0°
  2. customThe solution obtained
  3. waitwas left overnight at ambient temperature
  4. temperatureheated at 50°-55° C. for 1 hour
  5. temperatureunder reflux for 4 hours
  6. customThe cooled reaction solution
  7. customwas collected
  8. washwashed with water, air
  9. customdried
  10. temperatureheated
  11. temperatureunder reflux in acetic acid (85 ml.) for 12 hours
  12. temperatureThis mixture was cooled
  13. customthe solid residue removed by filtration
  14. customThe filtrate was evaporated
  15. customresidual acetic acid being removed by azeotropic evaporation with toluene (3×150 ml.)
  16. customThe oily residue obtained
  17. customabsorbed onto chromatographic silica gel (30 g.) by evaporation of the solvent
  18. additionThe residue was added to a column of silica gel (300 g.)
  19. washElution with an increasing concentration of ethyl acetate in toluene (up to 25% v/v) and
  20. customcombination and evaporation of those fractions
  21. additioncontaining the major component (relative flow value 0.6)

Sources & evidence

ORD record
ord-819b192c5cfc4e5f940c550a184fbc22
Source dataset
uspto-grants-1984_10
Patent number
US04478847

Reaction notes

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