Trifluoroacetic acid → 6-chloro-4'-[5-chloro-2-(1-methoxycarbonyl-cyclobutoxy)-phenyl]-2'-(5-fluoro-2-methyl-phenyl)-spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dione

HRID 658935

Reaction equation

HRID 658935 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]2([C:31]([O:33][CH3:34])=[O:32])[CH2:30][CH2:29][CH2:28]2)/[C:9]1=[O:35])=O)(C)(C)C.[F:36][C:37]1[CH:38]=[CH:39][C:40]([CH3:52])=[C:41]([CH:43]=[N:44][C:45]([O:47][Si](C)(C)C)=[CH2:46])[CH:42]=1.C(O)(C(F)(F)F)=O>C1(C)C=CC=CC=1>[Cl:17][C:14]1[CH:15]=[C:16]2[NH:8][C:9](=[O:35])[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]4([C:31]([O:33][CH3:34])=[O:32])[CH2:30][CH2:29][CH2:28]4)[CH2:46][C:45](=[O:47])[NH:44][CH:43]3[C:41]3[CH:42]=[C:37]([F:36])[CH:38]=[CH:39][C:40]=3[CH3:52])[C:11]2=[CH:12][CH:13]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 701785041-(5-Fluoro-2-methylphenyl)-3-trimethylsilyoxy-2-aza-1,3-butadieneHCID 86647006Z-6-chloro-3-[5-chloro-2-(1-methoxycarbonyl-cyclobutoxy)-benzylidene]-2-oxo-2,3-dihydro-indole-1-carboxylic acid tert-butyl ester

Product 1

HCID 765679126-chloro-4'-[5-chloro-2-(1-methoxycarbonyl-cyclobutoxy)-phenyl]-2'-(5-fluoro-2-methyl-phenyl)-spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dioneYield 11.5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of E/Z-6-chloro-3-[5-chloro-2-(1-methoxycarbonyl-cyclobutoxy)-benzylidene]-2-oxo-2,3-dihydro-indole-1-carboxylic acid tert-butyl ester (1.5 g, 2.9 mmol) and 1-(5-fluoro-2-methylphenyl)-3-trimethylsilyoxy-2-aza-1,3-butadiene (10 mmol) prepared in Example 4 in toluene (10 mL) was heated at 60° C. for 3 h. To the mixture was added TFA (5 mL), and the resultant solution was stirred at room temperature for 20 min, then concentrated in vacuo. The residue was partitioned between ethyl acetate and diluted aqueous NaOH solution. The organic layer was separated, washed with water, dried over anhydrous Na2SO4, and concentrated. The residue was purified by flash chromatography to give the title compound as white solid (200 mg).

Workup

  1. concentrationconcentrated in vacuo
  2. customThe residue was partitioned between ethyl acetate and diluted aqueous NaOH solution
  3. customThe organic layer was separated
  4. washwashed with water
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-a0dfb43cd7e2428fa3823597fc025c3a
Source dataset
uspto-grants-2011_12
Patent number
US08076482B2

Linked notes

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