6-Chloro-3-[5-chloro-2-(1-ethoxycarbonyl-1-methyl-ethoxy)-benzylidene]-2-oxo-2,3-dihydro-indole-1-carboxylic acid tert-butyl ester → racemic (2'R,3S,4'R)-6-chloro-4'-[5-chloro-2-(1-ethoxycarbonyl-1-methyl-ethoxy)-phenyl]-2'-(2,5-difluoro phenyl)spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dione

HRID 1728175Notes

Reaction equation

HRID 1728175 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:30]([O:32][CH2:33][CH3:34])=[O:31])([CH3:29])[CH3:28])[C:9]1=[O:35])=O)(C)(C)C.[F:36][C:37]1[CH:42]=[CH:41][C:40]([F:43])=[CH:39][C:38]=1[CH:44]=[N:45][C:46]([O:48][Si](C)(C)C)=[CH2:47]>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]([C:30]([O:32][CH2:33][CH3:34])=[O:31])([CH3:29])[CH3:28])[CH2:47][C:46](=[O:48])[NH:45][CH:44]3[C:38]3[CH:39]=[C:40]([F:43])[CH:41]=[CH:42][C:37]=3[F:36])[C:11]2=[CH:12][CH:13]=1

Participants

4

Reactant 2

HCID 671438546-Chloro-3-[5-chloro-2-(1-ethoxycarbonyl-1-methyl-ethoxy)-benzylidene]-2-oxo-2,3-dihydro-indole-1-carboxylic acid tert-butyl esterHCID 702041011-(2,5-Difluoro-phenyl)-3-trimethylsilyoxy-2-aza-1,3-butadiene

Product 1

HCID 76568094racemic (2'R,3S,4'R)-6-chloro-4'-[5-chloro-2-(1-ethoxycarbonyl-1-methyl-ethoxy)-phenyl]-2'-(2,5-difluoro phenyl)spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dioneYield 0.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

Under argon protection, 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 prepared in Example 229c (8 g, 15.4 mmol) and 1-(2,5-difluoro-phenyl)-3-trimethylsilyoxy-2-aza-1,3-butadiene (30.8 mmol) were dissolved in toluene. The solution was heated at 80° C. for 5 h. Then the solution was concentrated and the residue was purified by chromatography (CH2Cl2:CH3OH=50:1) to obtain 1.7 g crude product. The crude product (50 mg) was purified again by Prep-HPLC to obtain give title compound as a white solid (12 mg).

Workup

  1. concentrationThen the solution was concentrated
  2. customthe residue was purified by chromatography (CH2Cl2:CH3OH=50:1)
  3. customto obtain 1.7 g crude product
  4. customThe crude product (50 mg) was purified again by Prep-HPLC
  5. customto obtain

Sources & evidence

ORD record
ord-7281748d586943faaa34170f58e9e685
Source dataset
uspto-grants-2009_02
Patent number
US07495007B2

Reaction notes

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