Methanol → 6-chloro-2'-(3-chlorophenyl)-4'-phenyl spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dione

HRID 1727976Notes

Reaction equation

HRID 1727976 reaction equation
ClC1C=C2NC(=O)C3(C(CC(C)(C)C)[CH2:14][C:13](=[O:21])[NH:12][CH:11]3[C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([Cl:28])[CH:23]=3)C2=CC=1.C(OC([N:35]1[C:43]2[C:38](=[CH:39][CH:40]=[C:41]([Cl:44])[CH:42]=2)/[C:37](=[CH:45]/[C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)/[C:36]1=[O:52])=O)C.CO.[OH-].[Na+]>C1(C)C=CC=CC=1>[Cl:44][C:41]1[CH:42]=[C:43]2[NH:35][C:36](=[O:52])[C:37]3([CH:45]([C:46]4[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=4)[CH2:14][C:13](=[O:21])[NH:12][CH:11]3[C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([Cl:28])[CH:23]=3)[C:38]2=[CH:39][CH:40]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 14798Sodium HydroxideHCID 86615087Z-3-benzylidene-6-chloro-2-oxo-2,3-dihydro-indole-1-carboxylic acid ethyl esterHCID 1317273036-chloro-2'-(3-chlorophenyl)-4'-(2,2-dimethylpropyl) spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dione

Product 1

HCID 1317273136-chloro-2'-(3-chlorophenyl)-4'-phenyl spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dioneYield 100%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
140 °C

Procedure

To a solution of 1-(3-chlorophenyl)-3-trimethylsilyoxy-2-aza-1,3-butadiene prepared in example 1c in toluene (30 mL) was added E/Z-3-benzylidene-6-chloro-2-oxo-2,3-dihydro-indole-1-carboxylic acid ethyl ester prepared in Example 12b (0.4 g, 1.22 mmol). The reaction mixture was stirred under nitrogen in a sealed tube at 140° C. for 1 h. After the solution was cooled to room temperature, methanol (40 mL) was added. The reaction mixture was filtered through a short pad of celite gel and washed with ethyl acetate. The filtrate was concentrated. The residue was dissolved in methanol (30 mL) and 1N of NaOH solution (5 mL, 5 mmol) was added. The reaction mixture was stirred at room temperature for 0.5 h, then the mixture was concentrated. The residue was purified by chromatography (EtOAc:CH2Cl2=1:4) to give racemic (2′S,3S,4′R)-6-chloro-2′-(3-chlorophenyl)-4′-phenylspiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione as a yellow oil (Yield 0.5 g, 100%).

Workup

  1. temperatureAfter the solution was cooled to room temperature
  2. filtrationThe reaction mixture was filtered through a short pad of celite gel
  3. washwashed with ethyl acetate
  4. concentrationThe filtrate was concentrated
  5. dissolutionThe residue was dissolved in methanol (30 mL)
  6. stirringThe reaction mixture was stirred at room temperature for 0.5 h
  7. concentrationthe mixture was concentrated
  8. customThe residue was purified by chromatography (EtOAc:CH2Cl2=1:4)

Sources & evidence

ORD record
ord-30094670c3f1479b917cb712f59b89b0
Source dataset
uspto-grants-2009_02
Patent number
US07495007B2

Reaction notes

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