3-{[(2-Iodo-phenyl)-(3-phenyl-propynoyl)-amino]-methyl}-benzoic acid methyl ester → 3-{3-[4-methyl-1-phenyl-pent-(Z)-ylidene]-2-oxo-2,3-dihydro-indol-1-ylmethyl}-benzoic acid methyl ester

HRID 1623473Notes

Reaction equation

HRID 1623473 reaction equation
[CH3:1][O:2][C:3](=[O:29])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH2:10][N:11]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2I)[C:12](=[O:21])[C:13]#[C:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:5]=1.[Br-].[CH3:31][CH:32]([CH3:36])[CH2:33][CH2:34][Zn+]>C(Cl)Cl.C(OCC)(=O)C>[CH3:1][O:2][C:3](=[O:29])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH2:10][N:11]2[C:22]3[C:27](=[CH:26][CH:25]=[CH:24][CH:23]=3)/[C:13](=[C:14](/[C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)\[CH2:34][CH2:33][CH:32]([CH3:36])[CH3:31])/[C:12]2=[O:21])[CH:5]=1

Participants

5

Reactant 2

HCID 670363063-{[(2-Iodo-phenyl)-(3-phenyl-propynoyl)-amino]-methyl}-benzoic acid methyl esterHCID 178445882HCID 178445882, compound

Product 1

HCID 510344403-{3-[4-methyl-1-phenyl-pent-(Z)-ylidene]-2-oxo-2,3-dihydro-indol-1-ylmethyl}-benzoic acid methyl esterYield 28%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

To a degassed refluxing solution of 3-{[(2-iodo-phenyl)-(3-phenyl-propynoyl)-amino]-methyl}-benzoic acid methyl ester (100 mg, 0.2 mmol) and Ni(PPh3)2I2 (16 mg, 0.02 mmol) in CH2Cl2 (8 ml) was added 3-methylbutylzinc bromide (151 mg, 0.7 mmol) in CH2Cl2 (1 ml). The reaction was stirred at 40° C. for 6 h and then the solution was cooled to room temperature. The resultant solution was diluted with ethyl acetate (50 ml). The organic layer was washed with aqueous HCl solution (4%, 10 ml), brine (3×10 ml). The aqueous layer was back-extracted with ethyl acetate (3×10 ml). The combined organic layer was dried over anhydrous sodium sulfate. After filtration, the solvent was removed under reduced pressure and the residue was purified by column chromatography on silica gel, eluting with petrol ether-ethyl acetate, to give 3-{3-[4-methyl-1-phenyl-pent-(Z)-ylidene]-2-oxo-2,3-dihydro-indol-1-ylmethyl}-benzoic acid methyl ester (24 mg, 28%) as light yellow solid. 1H NMR (300 Hz, CDCl3): δppm 0.88 (d, 6H), 1.43-1.55 (m, 2H), 1.68-1.72 (m, 1H), 2.93-2.99 (m, 2H), 3.91 (s, 3H), 4.89 (s, 2H), 6.64 (d, 1H), 7.05 (t, 1H), 7.15 (t, 1H), 7.28-7.38 (m, 4H), 7.40-7.47 (m, 3H), 7.62 (d, 1H), 7.91 (d, 1H), 7.95 (s, 1H); and 3-{3-[4-methyl-1-phenyl-pent-(E)-ylidene]-2-oxo-2,3-dihydro-indol-1-ylmethyl}-benzoic acid methyl ester (29 mg, 33%) as light yellow solid. 1H NMR (300 Hz, CDCl3): δ ppm 0.88 (d, 6H), 1.36-1.44 (m, 2H), 1.64-1.68 (m, 1H), 3.33-3.38 (m, 2H), 3.91 (s, 3H), 5.04 (s, 2H), 6.01 (d, 1H), 6.58-6.61 (m, 2H), 6.96-7.02 (t, 1H), 7.26-7.29 (m, 2H), 7.37 (t, 2H), 7.43-7.52 (m, 3H), 7.93 (d, 1H), 8.03 (s, 1H).

Workup

  1. temperaturethe solution was cooled to room temperature
  2. washThe organic layer was washed with aqueous HCl solution (4%, 10 ml), brine (3×10 ml)
  3. extractionThe aqueous layer was back-extracted with ethyl acetate (3×10 ml)
  4. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
  5. filtrationAfter filtration
  6. customthe solvent was removed under reduced pressure
  7. customthe residue was purified by column chromatography on silica gel
  8. washeluting with petrol ether-ethyl acetate

Sources & evidence

ORD record
ord-da3ef55dd16a452aa03b7050c04dbe93
Source dataset
uspto-grants-2014_07
Patent number
US08778973B2

Reaction notes

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