Methane → 1'-[4-Bromo-2-fluorobenzyl]-7'-chloro-spiro[imidazolidine-4,3'-indoline]-2,2',5-trione

HRID 64956Notes

Reaction equation

HRID 64956 reaction equation
[Br:1][C:2]1[CH:20]=[CH:19][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][C:14]=3[Cl:16])[C:9](=O)[C:8]2=[O:18])=[C:4]([F:21])[CH:3]=1.[C-]#N.[K+].[C:25](=[O:28])([O-])[O-].[NH4+:29].[NH4+:30].C.[CH2:32]([OH:34])C>O>[Br:1][C:2]1[CH:20]=[CH:19][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][C:14]=3[Cl:16])[C:9]3([C:32](=[O:34])[NH:30][C:25](=[O:28])[NH:29]3)[C:8]2=[O:18])=[C:4]([F:21])[CH:3]=1

Participants

7

Reactant 5

HCID 297MethaneHCID 702EthanolHCID 9032Potassium CyanideHCID 517111Ammonium CarbonateHCID 132480821-[(4-Bromo-2-fluorophenyl)methyl]-7-chloro-1H-indole-2,3-dione

Product 1

HCID 136911461'-[4-Bromo-2-fluorobenzyl]-7'-chloro-spiro[imidazolidine-4,3'-indoline]-2,2',5-trione

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A stirred suspension of 1-(4-bromo-2-fluorobenzyl)-7-chloro-indoline-2,3-dione (96 g.) in ethanol (1500 ml.) was treated with a solution of potassium cyanide (21.0 g.) and ammonium carbonate (300 g.) in water (1500 ml.). The mixture was stirred at 45°-50° C. for 4 hours. Activated charcoal (50 g.) was added and the mixture was stirred for a further hour at 45°-50° C. The hot mixture was filtered through diatomaceous earth and the filter cake was washed with aqueous ethanol (2×200 ml.; 1:1 v/v) at 60° C. The cooled filtrate was made acid to pH 4 at 0°-5° C. with 10M hydrochloric acid and the precipitated solid was collected by filtration, washed with water and dried. Recrystallisation twice from 1:1 v/v ethyl acetate/petroleum ether, b.p. 60°-80° C. gave (±)-1'-(4-bromo-2-fluoro-benzyl)-7'-chloro-spiro-(imidazolidine-4,3'-indoline)2,2',5-trione (60 g.) m.p. 240°-242° C.

Workup

  1. stirringthe mixture was stirred for a further hour at 45°-50° C
  2. filtrationThe hot mixture was filtered through diatomaceous earth
  3. washthe filter cake was washed with aqueous ethanol (2×200 ml.; 1:1 v/v) at 60° C
  4. customat 0°-5° C.
  5. filtrationthe precipitated solid was collected by filtration
  6. washwashed with water
  7. customdried
  8. customRecrystallisation twice from 1:1 v/v ethyl acetate/petroleum ether, b.p. 60°-80° C.

Sources & evidence

ORD record
ord-dc283e670399417fa5f918eb9e5e1526
Source dataset
uspto-grants-1986_09
Patent number
US04611062

Reaction notes

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