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 504452Notes

Reaction equation

HRID 504452 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:17])=[C:6]([CH:8]=[N:9][C:10]([O:12][Si](C)(C)C)=[CH2:11])[CH:7]=1.C(OC([N:25]1[C:33]2[C:28](=[CH:29][CH:30]=[C:31]([Cl:34])[CH:32]=2)[C:27](=[CH:35][C:36]2[CH:41]=[C:40]([Cl:42])[CH:39]=[CH:38][C:37]=2[O:43][C:44]2([C:48]([O:50][CH3:51])=[O:49])[CH2:47][CH2:46][CH2:45]2)[C:26]1=[O:52])=O)(C)(C)C.C(O)(C(F)(F)F)=O>C1(C)C=CC=CC=1>[Cl:34][C:31]1[CH:32]=[C:33]2[NH:25][C:26](=[O:52])[C:27]3([CH:35]([C:36]4[CH:41]=[C:40]([Cl:42])[CH:39]=[CH:38][C:37]=4[O:43][C:44]4([C:48]([O:50][CH3:51])=[O:49])[CH2:45][CH2:46][CH2:47]4)[CH2:12][C:10](=[O:11])[NH:9][CH:8]3[C:6]3[CH:7]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=3[CH3:17])[C:28]2=[CH:29][CH:30]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 57565913HCID 57565913, compoundHCID 701785041-(5-Fluoro-2-methylphenyl)-3-trimethylsilyoxy-2-aza-1,3-butadiene

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)-dione

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
80 °C

Procedure

To a toluene solution of 1-(5-fluoro-2-methylphenyl)-3-trimethylsilyoxy-2-aza-1,3-butadiene in toluene (2 M, 5 mL, 10 mmol) was added 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). The reaction mixture was heated at 80° C. overnight under argon protection, then TFA (5 mL) was added, and the resulting mixture was stirred at room temperature for 20 min, evaporated in vacuo. The residue was partitioned between ethyl acetate and NaOH aq. (1 M). The organic layer was washed with water, dried over anhydrous Na2SO4, concentrated and purified by column chromatography to give the title compound as a white solid (340 mg).

Workup

  1. customevaporated in vacuo
  2. customThe residue was partitioned between ethyl acetate and NaOH aq. (1 M)
  3. washThe organic layer was washed with water
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationconcentrated
  6. custompurified by column chromatography

Sources & evidence

ORD record
ord-57e54d8bf91d4e21979cdfb6b4e795c9
Source dataset
uspto-grants-2010_08
Patent number
US07776875B2

Reaction notes

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