Ammonium Chloride → 6-chloro-4'-(3-chlorophenyl)-2'-(1-ethyl-1-hydroxy-propyl)spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dione

HRID 1728049Notes

Reaction equation

HRID 1728049 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:28])[C:10]3([CH:15]([C:16]4[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[CH:17]=4)[CH2:14][C:13](=[O:23])[NH:12][CH:11]3[C:24](=[O:27])[CH2:25][CH3:26])[C:5]2=[CH:4][CH:3]=1.[CH2:29]([Mg]Cl)[CH3:30].[NH4+].[Cl-]>O1CCCC1>[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:28])[C:10]3([CH:15]([C:16]4[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[CH:17]=4)[CH2:14][C:13](=[O:23])[NH:12][CH:11]3[C:24]([CH2:29][CH3:30])([OH:27])[CH2:25][CH3:26])[C:5]2=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 76568170HCID 76568170, compoundHCID 178461633HCID 178461633, compound

Product 1

HCID 765680146-chloro-4'-(3-chlorophenyl)-2'-(1-ethyl-1-hydroxy-propyl)spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dioneYield 93.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of racemic (2′R,3R,4′S)-6-chloro-4′-(3-chlorophenyl)-2′-propionylspiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione (100 mg, 0.24 mmol) prepared in example 103 in tetrahydrofuran (3 mL) at −78° C. was added a tetrahydrofuran solution of ethylmagnesium chloride (2M, 6 mL, 12 mmol). The reaction mixture was stirred at −78° C. for 0.5 h, then slowly warmed to room temperature and stirred for 2 h. The mixture was poured into saturated aqueous NH4Cl solution, and the mixture was extracted with ethyl acetate. The organic layer was separated, dried over MgSO4, concentrated. The residue was purified by chromatography (EtOAc:MeOH=10:1) to give racemic (2′R,3R,4′S)-6-chloro-4′-(3-chlorophenyl)-2′-(1-ethyl-1-hydroxy-propyl)spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione as a white solid (Yield 100 mg, 93%)

Workup

  1. temperatureslowly warmed to room temperature
  2. stirringstirred for 2 h
  3. extractionthe mixture was extracted with ethyl acetate
  4. customThe organic layer was separated
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customThe residue was purified by chromatography (EtOAc:MeOH=10:1)

Sources & evidence

ORD record
ord-d8e6517fa2334e66b5ff9259661aa145
Source dataset
uspto-grants-2009_02
Patent number
US07495007B2

Reaction notes

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