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

HRID 1380294Notes

Reaction equation

HRID 1380294 reaction equation
[Br:1][C:2]1[CH:25]=[CH:24][C:5]([CH2:6][N:7]2[C:15]3[C:14]([Cl:16])=[CH:13][C:12](=O)[CH2:11][C:10]=3[C:9]3([CH2:21][NH:20][C:19](=[O:22])[NH:18]3)[C:8]2=[O:23])=[C:4]([F:26])[CH:3]=1.Cl.[OH-:28].C[N+](C(C1C=CC=CC=1)C)(C)C>CO>[Br:1][C:2]1[CH:25]=[CH:24][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:21](=[O:28])[NH:20][C:19](=[O:22])[NH:18]3)[C:8]2=[O:23])=[C:4]([F:26])[CH:3]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 13056022HCID 13056022, compoundHCID 70352137HCID 70352137, compound

Product 1

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

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
70 °C

Procedure

(±)-1'-(4-Bromo-2-fluorobenzyl)-7'-chloro-spiro[imidazoline-4,3'-indoline]-2,2',5'-trione (64.4 g.) was dissolved in a 0.253 M solution of (-)-N,N,N-trimethyl-(1-phenylethyl)ammonium hydroxide in methanol (581 ml.). The solution was filtered and the filtrate was evaporated. The residue was dissolved in 2-methoxyethanol (132 ml.). The solution was warmed to 70° C. and then diluted with 1,2-dimethoxyethane (440 ml.) previously warmed to 70° C. The clear solution was stored at 0° C. for 48 hours and the crystals of the quaternary ammonium salt were collected by filtration [27 g.; [α]D23 +21.1°, c. 0.93, MeOH)]. This product was recrystallised from 2-methoxyethanol (55.3 ml.) and 1,2-dimethoxyethane (184 ml.) to give crystals [20 g.; [α]D23 +22° (c.1.11, MeOH)]. A third recrystallisation gave crystals [15.8 g.; [α]D23 +21.9° (c.1.12 MeOH)]. The crystalline salt (15.8 g.) thus obtained was dissolved in methanol (50 ml.) and treated with 0.25 M aqueous hydrochloric acid (105 ml.). The solution was chilled at 0° C. overnight and the solid removed by filtration, washed with water and dried over phosphorus pentoxide under vacuum to give the (+)-enantiomer of 1'-[4-bromo-2-fluorobenzyl]-7'-chloro-spiro[imidazolidine-4,3'-indoline]-2,2',5-trione (9.1 g.), m.p. 260°-262° C., [α]D23 +17.9° (c. 0.89, MeOH).

Workup

  1. filtrationThe solution was filtered
  2. customthe filtrate was evaporated
  3. dissolutionThe residue was dissolved in 2-methoxyethanol (132 ml.)
  4. additiondiluted with 1,2-dimethoxyethane (440 ml.)
  5. temperaturepreviously warmed to 70° C
  6. filtrationthe crystals of the quaternary ammonium salt were collected by filtration [27 g
  7. customThis product was recrystallised from 2-methoxyethanol (55.3 ml.) and 1,2-dimethoxyethane (184 ml.)
  8. customto give crystals [20 g.; [α]D23 +22° (c.1.11, MeOH)]
  9. customA third recrystallisation
  10. customgave crystals [15.8 g.; [α]D23 +21.9° (c.1.12 MeOH)]
  11. customThe crystalline salt (15.8 g.) thus obtained
  12. temperatureThe solution was chilled at 0° C. overnight
  13. customthe solid removed by filtration
  14. washwashed with water
  15. dry with materialdried over phosphorus pentoxide under vacuum

Sources & evidence

ORD record
ord-99527a83af464ec781f2ffe13ad7ce03
Source dataset
uspto-grants-1986_04
Patent number
US04581366

Reaction notes

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