Toluene → 6-chloro-4'-[5-chloro-2-(1-ethoxycarbonyl-1-methyl-ethoxy)-phenyl]-2'-(5-fluoro-2-methyl phenyl) spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dione

HRID 504440Notes

Reaction equation

HRID 504440 reaction equation
C1(C)C=CC=CC=1.[F:8][C:9]1[CH:10]=[CH:11][C:12]([CH3:24])=[C:13]([CH:15]=[N:16][C:17]([O:19][Si](C)(C)C)=[CH2:18])[CH:14]=1.C(OC([N:32]1[C:40]2[C:35](=[CH:36][CH:37]=[C:38]([Cl:41])[CH:39]=2)[C:34](=[CH:42][C:43]2[CH:48]=[C:47]([Cl:49])[CH:46]=[CH:45][C:44]=2[O:50][C:51]([C:54]([O:56][CH2:57][CH3:58])=[O:55])([CH3:53])[CH3:52])[C:33]1=[O:59])=O)(C)(C)C>CO>[Cl:41][C:38]1[CH:39]=[C:40]2[NH:32][C:33](=[O:59])[C:34]3([CH:42]([C:43]4[CH:48]=[C:47]([Cl:49])[CH:46]=[CH:45][C:44]=4[O:50][C:51]([C:54]([O:56][CH2:57][CH3:58])=[O:55])([CH3:53])[CH3:52])[CH2:19][C:17](=[O:18])[NH:16][CH:15]3[C:13]3[CH:14]=[C:9]([F:8])[CH:10]=[CH:11][C:12]=3[CH3:24])[C:35]2=[CH:36][CH:37]=1

Participants

5

Reactant 3

HCID 1140TolueneHCID 671438546-Chloro-3-[5-chloro-2-(1-ethoxycarbonyl-1-methyl-ethoxy)-benzylidene]-2-oxo-2,3-dihydro-indole-1-carboxylic acid tert-butyl esterHCID 701785041-(5-Fluoro-2-methylphenyl)-3-trimethylsilyoxy-2-aza-1,3-butadiene

Product 1

HCID 765678816-chloro-4'-[5-chloro-2-(1-ethoxycarbonyl-1-methyl-ethoxy)-phenyl]-2'-(5-fluoro-2-methyl phenyl) spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dioneYield 29.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
130 °C

Procedure

To a toluene solution (50 mL) of 1-(5-fluoro-2-methyl-phenyl)-3-trimethylsilyoxy-2-aza-1,3-butadiene (77 mmol) was added E/Z 6-chloro-3-[5-chloro-2-(1-ethoxycarbonyl-1-methyl-ethoxy)-benzylidene]-2-oxo-2,3-dihydro-indole-1-carboxylic acid tert-butyl ester (8 g, 15.44 mmol). Then the reaction mixture were heated at 130° C. for 2. After the solution was cooled to room temperature, methanol was added, and then the mixture was concentrated. Then a mixture of trifluoroacetic acid (10 mL) and dichloromethane (30 mL) was added. The reaction mixture was stirred at room temperature for 10 min. The solution was concentrated and the residue was purified by Prep-HPLC to give title compound as a white solid (2.7 g).

Workup

  1. temperatureAfter the solution was cooled to room temperature
  2. concentrationthe mixture was concentrated
  3. additionThen a mixture of trifluoroacetic acid (10 mL) and dichloromethane (30 mL)
  4. additionwas added
  5. concentrationThe solution was concentrated
  6. customthe residue was purified by Prep-HPLC

Sources & evidence

ORD record
ord-65cb4171de0240f78ff3d896b4ad5edb
Source dataset
uspto-grants-2010_08
Patent number
US07776875B2

Reaction notes

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