Sodium Hydroxide → (2'S,3R,4'E,6'S)-6-bromo-2'-(3-chlorophenyl)-4'-hydroxyimino-6'-methoxyspiro[1H-indole-3,1'-cyclohexane]-2-one

HRID 1987800Notes

Reaction equation

HRID 1987800 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]3([CH:16]([O:17][CH3:18])[CH2:15][C:14](=O)[CH2:13][CH:12]3[C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[CH:21]=3)[C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1.[OH-:27].[NH4+:28].Cl.[OH-].[Na+]>CCO>[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([C@:6]3([C@@H:16]([O:17][CH3:18])[CH2:15]/[C:14](=[N:28]/[OH:27])/[CH2:13][C@H:12]3[C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[CH:21]=3)[C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 13908798HCID 13908798, compoundHCID 68903423Rac-(1r,2s,6s)-6'-bromo-2-(3-chlorophenyl)-6-methoxyspiro[cyclohexane-1,3'-[3h]indole]-2',4(1'h)-dione

Product 1

HCID 57724966(2'S,3R,4'E,6'S)-6-bromo-2'-(3-chlorophenyl)-4'-hydroxyimino-6'-methoxyspiro[1H-indole-3,1'-cyclohexane]-2-oneYield 46%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To the suspension of rac-(1R,2S,6S)-6′-bromo-2-(3-chlorophenyl)-6-methoxyspiro[cyclohexane-1,3′-[3H]indole]-2′,4(1′H)-dione (1.69 g, 3.89 mmol) and NH4OH—HCl (0.27 g, 3.89 mmol) in EtOH (40 mL) was added a queous NaOH solution (1N, 4 mL, 4 mmol). The reaction mixture was heated at reflux for 1 h. TLC analysis indicated the formation of desired product and complete consumption of starting material. The reaction was cooled to room temperature, and water was added. The mixture was extracted with ethyl acetate. The organic layer was separated, dried over MgSO4, and concentrated. The residue was purified by chromatography (EtOAc:hexanes=1:3, 1:2, then 1:1) to give the less polar product rac-E-(1R,2S,6S)-6′-bromo-2-(3-chlorophenyl)-6-methoxy spiro[cyclohexane-1,3′-[3H]indole]-2′,4(1′H)-dione-4-oxime as a white solid (0.8 g, 46%): HRMS (ES+) m/z Calcd for C22H18BrClN2O3+H [(M+H)+]: 449.0262, Found: 449.0260; rac-Z-(1R,2S,6S)-6′-bromo-2-(3-chlorophenyl)-6-methoxy spiro[cyclohexane-1,3′-[3H]indole]-2′,4(1′H)-dione-4-oxime as a white solid (0.8 g, 46%): HRMS (ES+) m/z Calcd for C22H18BrClN2O3+H [(M+H)+]: 449.0262, Found: 449.0261.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 1 h
  3. customthe formation of desired product and complete consumption of starting material
  4. additionwater was added
  5. extractionThe mixture was extracted with ethyl acetate
  6. customThe organic layer was separated
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. customThe residue was purified by chromatography (EtOAc

Sources & evidence

ORD record
ord-5d881a2198594b03a08f4dcc0b645fcb
Source dataset
uspto-grants-2009_06
Patent number
US07553833B2

Reaction notes

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