Z-6-chloro-3-(3-chloro-benzylidene)-2-oxo-2,3-dihydro-indole-1-carboxylic acid tert-butyl ester → racemic (2'R,3R,4'S)-6-chloro-4'-(3-chlorophenyl)-2'-(3-iodophenyl)spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dione

HRID 1728126Notes

Reaction equation

HRID 1728126 reaction equation
[I:1][C:2]1[CH:3]=[C:4]([CH:8]=[N:9][C:10]([O:12][Si](C)(C)C)=[CH2:11])[CH:5]=[CH:6][CH:7]=1.C(OC([N:24]1[C:32]2[C:27](=[CH:28][CH:29]=[C:30]([Cl:33])[CH:31]=2)/[C:26](=[CH:34]/[C:35]2[CH:40]=[CH:39][CH:38]=[C:37]([Cl:41])[CH:36]=2)/[C:25]1=[O:42])=O)(C)(C)C>C1(C)C=CC=CC=1>[Cl:33][C:30]1[CH:31]=[C:32]2[NH:24][C:25](=[O:42])[C:26]3([CH:34]([C:35]4[CH:40]=[CH:39][CH:38]=[C:37]([Cl:41])[CH:36]=4)[CH2:12][C:10](=[O:11])[NH:9][CH:8]3[C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([I:1])[CH:3]=3)[C:27]2=[CH:28][CH:29]=1

Participants

4

Reactant 2

HCID 66640668Z-6-chloro-3-(3-chloro-benzylidene)-2-oxo-2,3-dihydro-indole-1-carboxylic acid tert-butyl esterHCID 765681791-(3-Iodophenyl)-3-trimethylsilyoxy-2-aza-1,3-butadiene

Product 1

HCID 76568101racemic (2'R,3R,4'S)-6-chloro-4'-(3-chlorophenyl)-2'-(3-iodophenyl)spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dioneYield 77.7%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
140 °C

Procedure

To a solution of 1-(3-iodophenyl)-3-trimethylsilyoxy-2-aza-1,3-butadiene prepared in example 192a (1.2 g, 3.5 mmol) in toluene (40 mL) was added E/Z-6-chloro-3-(3-chlorobenzylidene)-2-oxo-2,3-dihydro-indole-1-carboxylic acid tert-butyl ester prepared in Example 24a (0.5 g, 1.28 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 and concentrated. The residue was dissolved in dichloromethane (20 mL) and trifluoroactic acid (10 mL) was added. After the reaction mixture was stirred at room temperature for 0.5 h, the mixture was concentrated. The residue was partitioned between saturated NaHCO3 solution and ethyl acetate. The aqueous layer was extracted with ethyl acetate. The combined organic layer was dried over Na2SO4 and concentrated. The residue was purified by chromatography (EtOAc:CH2Cl2=1:3 then 1:2) to give racemic (2′R,3R,4′S)-6-chloro-4′-(3-chlorophenyl)-2′-(3-iodophenyl)spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione as a white solid (Yield 0.56 g, 77%).

Workup

  1. temperatureAfter the solution was cooled to room temperature
  2. concentrationconcentrated
  3. dissolutionThe residue was dissolved in dichloromethane (20 mL)
  4. additiontrifluoroactic acid (10 mL) was added
  5. stirringAfter the reaction mixture was stirred at room temperature for 0.5 h
  6. concentrationthe mixture was concentrated
  7. customThe residue was partitioned between saturated NaHCO3 solution and ethyl acetate
  8. extractionThe aqueous layer was extracted with ethyl acetate
  9. dry with materialThe combined organic layer was dried over Na2SO4
  10. concentrationconcentrated
  11. customThe residue was purified by chromatography (EtOAc

Sources & evidence

ORD record
ord-dfcd3b9690ba4bd092f483710ba03b19
Source dataset
uspto-grants-2009_02
Patent number
US07495007B2

Reaction notes

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