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

HRID 658921Notes

Reaction equation

HRID 658921 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]([CH2:34][CH3:35])([C:30]([O:32][CH3:33])=[O:31])[CH2:28][CH3:29])/[C:9]1=[O:36])=O)(C)(C)C.[Cl: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:30]([O:32][CH3:33])=[O:31])[CH2:34][CH3:35])[CH2:47][C:46](=[O:48])[NH:45][CH:44]3[C:42]3[CH:43]=[C:38]([Cl:37])[CH:39]=[CH:40][C:41]=3[CH3:53])[C:11]2=[CH:12][CH:13]=1

Participants

4

Reactant 2

HCID 702039431-(5-Chloro-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 722961904'-[5-chloro-2-(1-ethyl-1-methoxycarbonyl-propoxy)-phenyl]-6-chloro-2'-(5-chloro-2-methyl-phenyl)spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dioneYield 19.4%

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 (2.63 g, 4.9 mmol) prepared in Example 16 and 1-(5-chloro-2-methylphenyl)-3-trimethylsilyoxy-2-aza-1,3-butadiene (20 mmol) in toluene (20 mL) was heated at 60° C. for 3 h, and concentrated in vacuo. To the residue was added DCM (20 mL) and TFA (10 mL), and the resulting solution was stirred at room temperature for 3 h, then concentrated, 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 column chromatography to give the title compound as white solid (600 mg).

Workup

  1. concentrationconcentrated in vacuo
  2. additionTo the residue was added DCM (20 mL) and TFA (10 mL)
  3. concentrationconcentrated
  4. custompartitioned between ethyl acetate and diluted aqueous NaOH solution
  5. customThe organic layer was separated
  6. washwashed with water
  7. dry with materialdried over anhydrous Na2SO4
  8. concentrationconcentrated
  9. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-74abb2359fad4efba4031f2f9fe66766
Source dataset
uspto-grants-2011_12
Patent number
US08076482B2

Reaction notes

Loading…