1-(5-Fluoro-2-methylphenyl)-3-trimethylsilyoxy-2-aza-1,3-butadiene → 6-chloro-4'-[5-chloro-2-(1-ethyl-1-methoxycarbonyl-propoxy)-phenyl]-2'-(5-fluoro-2-methyl-phenyl) spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dione

HRID 658914Notes

Reaction equation

HRID 658914 reaction equation
C(OC([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([Cl:17])[CH:15]=2)/[C:10](=[CH:18]/[C:19]2[CH:24]=[C:23]([Cl:25])[CH:22]=[CH:21][C:20]=2[O:26][C:27]([C:32]([O:34][CH3:35])=[O:33])([CH2:30][CH3:31])[CH2:28][CH3:29])/[C:9]1=[O:36])=O)(C)(C)C.[F:37][C:38]1[CH:39]=[CH:40][C:41]([CH3:53])=[C:42]([CH:44]=[N:45][C:46]([O:48][Si](C)(C)C)=[CH2:47])[CH:43]=1>C1(C)C=CC=CC=1>[Cl:17][C:14]1[CH:15]=[C:16]2[NH:8][C:9](=[O:36])[C:10]3([CH:18]([C:19]4[CH:24]=[C:23]([Cl:25])[CH:22]=[CH:21][C:20]=4[O:26][C:27]([CH2:28][CH3:29])([C:32]([O:34][CH3:35])=[O:33])[CH2:30][CH3:31])[CH2:47][C:46](=[O:48])[NH:45][CH:44]3[C:42]3[CH:43]=[C:38]([F:37])[CH:39]=[CH:40][C:41]=3[CH3:53])[C:11]2=[CH:12][CH:13]=1

Participants

4

Reactant 2

HCID 701785041-(5-Fluoro-2-methylphenyl)-3-trimethylsilyoxy-2-aza-1,3-butadieneHCID 86632089Z-3-[5-chloro-2-(1-ethyl-1-methoxycarbonyl-propoxy)-benzylidene]-6-chloro-2-oxo-2,3-dihydro-indole-1-carboxylic acid tert-butyl ester

Product 1

HCID 722961936-chloro-4'-[5-chloro-2-(1-ethyl-1-methoxycarbonyl-propoxy)-phenyl]-2'-(5-fluoro-2-methyl-phenyl) spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dioneYield 23.9%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of E/Z-3-[5-chloro-2-(1-methoxycarbonyl-1-ethyl-propoxy)-benzylidene]-6-chloro-2-oxo-2,3-dihydro-indole-1-carboxylic acid tert-butyl ester (7.6 g, 15 mmol) and 1-(5-fluoro-2-methyl-phenyl)-3-trimethylsilyoxy-2-aza-1,3-butadiene (60 mmol) prepared in Example 4 in toluene (60 mL) was heated at 60° C. for 3 h, and concentrated in vacuo. To the residue was added DCM (50 mL) and TFA (20 mL), and the resulting solution was stirred at room temperature for 3 h, then concentrated in vacuo, partitioned between ethyl acetate and diluted aqueous NaOH solution. The organic layer was washed with water, dried over anhydrous Na2SO4, and concentrated. The residue was purified by flash column chromatography to give the title compound as white solid (2.2 g).

Workup

  1. concentrationconcentrated in vacuo
  2. additionTo the residue was added DCM (50 mL) and TFA (20 mL)
  3. concentrationconcentrated in vacuo
  4. custompartitioned between ethyl acetate and diluted aqueous NaOH solution
  5. washThe organic layer was washed with water
  6. dry with materialdried over anhydrous Na2SO4
  7. concentrationconcentrated
  8. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-0f42fde241724ea19dbb21eb5e23bf22
Source dataset
uspto-grants-2011_12
Patent number
US08076482B2

Reaction notes

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