Triethylamine → 3-(1-Benzenesulfonyl-1H-indol-5-yl)-but-2-enoic acid methyl ester

HRID 1394616Notes

Reaction equation

HRID 1394616 reaction equation
I[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([S:11]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)(=[O:13])=[O:12])[CH:6]=[CH:5]2.[C:20]([O:25][CH3:26])(=[O:24])/[CH:21]=[CH:22]/[CH3:23].C(N(CC)CC)C.[I-]>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C.CCCCCC>[CH3:26][O:25][C:20](=[O:24])[CH:21]=[C:22]([C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([S:11]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)(=[O:13])=[O:12])[CH:6]=[CH:5]2)[CH3:23]

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 30165Iodide IonHCID 638132Methyl Crotonate2×HCID 179527921-benzenesulfonyl-5-iodo-1H-indole

Product 1

HCID 692189243-(1-Benzenesulfonyl-1H-indol-5-yl)-but-2-enoic acid methyl esterYield 109.6%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

5-Iodo-N-benzenesulfonylindole (18.09 g, 47 mmol), methyl crotonate (40 mL, 378 mmol), triethylamine (145 mL), and palladium acetate (2.65 g, 11.8 mmol) were combined in DMF (600 mL). The reaction was heated at 100° C. for 4 h. TLC (3:1) hexane:ethyl acetate showed iodide still present. Methyl crotonate (25 mL) and dichlorobis(triphenylphosphine) palladium(II) (3.31 g, 4.7 mmol) was added. The reaction was heated for an additional 4 h and then at room temperature for 13 h at which time starting material was virtually gone. The solids were allowed to settle and most of the liquid decanted off. The remaining portion was filtered through a pad of celite to remove the solids and the volume reduced somewhat in vacuo. The solution was diluted with water (1 L) and washed with diethyl ether (3×500 mL). The organic portion was washed with 1N HCl (2×500 mL), brine (2×500 mL), dried (MgSO4), filtered and evaporated in vacuo to provide 18.3 g of a dark brown oil. The material was purified preparatively in two runs on a Waters 2000LC using a gradient elution of (98:2) ethyl acetate:hexane to 66:34 ethyl acetate:hexane to give 6.79 g (40%). Mp: 80-85° C.

Workup

  1. temperatureThe reaction was heated for an additional 4 h
  2. customdecanted off
  3. filtrationThe remaining portion was filtered through a pad of celite
  4. customto remove the solids
  5. additionThe solution was diluted with water (1 L)
  6. washwashed with diethyl ether (3×500 mL)
  7. washThe organic portion was washed with 1N HCl (2×500 mL), brine (2×500 mL)
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. customevaporated in vacuo

Sources & evidence

ORD record
ord-eb3718d4f3f342bcb25602f0ee9556e2
Source dataset
uspto-grants-2008_03
Patent number
US07348359B2

Reaction notes

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