Methyl Acrylate → HCID 13598799, compound

HRID 1260163Notes

Reaction equation

HRID 1260163 reaction equation
Br[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][CH:8]=[CH:7]2.[C:11]([O:15][CH3:16])(=[O:14])[CH:12]=[CH2:13].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)C(C)C)(C)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C)C=O>[NH:9]1[C:10]2[C:6](=[CH:5][CH:4]=[CH:3][C:2]=2/[CH:13]=[CH:12]/[C:11]([O:15][CH3:16])=[O:14])[CH:7]=[CH:8]1

Participants

7

Reactant 4

HCID 7294Methyl Acrylate3×HCID 11776Triphenylphosphine3×HCID 81531DiisopropylethylamineHCID 27570207-Bromoindole

Product 1

HCID 13598799HCID 13598799, compoundYield 67.4%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalyst3×HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

7-Bromoindole (5.0 g, 25.5 mmol), methyl acrylate (4.6 ml, 51.1 mmol), triphenylphosphine (0.55 g, 2.10 mmol), N,N-diisopropylethylamine (5.8 ml, 42.3 mmol), and palladium (II) acetate (0.25 g, 1.11 mmol) were added to N,N-dimethylformamide (50 ml), and the mixture was stirred at 70° C. for 18 hours under a stream of nitrogen. After cooling to room temperature, methyl acrylate (4.6 ml, 51.1 mmol), triphenylphosphine (0.55 g, 2.10 mmol), and palladium (II) acetate (0.25 g, 1.11 mmol) were added to the reaction mixture, and the mixture was stirred at 75° C. for 47 hours under a stream of nitrogen. After cooling to room temperature, methyl acrylate (7.0 ml, 77.7 mmol), triphenylphosphine (0.88 g, 3.36 mmol), and palladium (II) acetate (0.40 g, 1.78 mmol) were added to the reaction mixture, and the mixture was stirred at 100° C. for 95 hours under a stream of nitrogen. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. To the obtained residue, a hexane/ethyl acetate mixed solution (1:1, 300 ml) was added, and the organic layer was washed with water. The obtained aqueous layer was subjected to extraction with a hexane/ethyl acetate (1:1) mixed solution, and the combined organic layer was washed with saturated saline. The obtained organic layer was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The obtained residue was purified by silica gel chromatography (eluent; hexane:ethyl acetate=6:1) to obtain 2 (E)-methyl 3-(1H-indol-7-yl)acrylate (3.46 g, 67%) as a pale yellow-brown solid. ESI-MS: m/z 202 [M+H]+. 1H-NMR (CDCl3) δ: 3.85 (3H, s), 6.52 (1H, d, J=16.0 Hz), 6.62 (1H, dd, J=2.9, 2.0 Hz), 7.16 (1H, t, J=7.6 Hz), 7.28 (1H, t, J=2.9 Hz), 7.43 (1H, d, J=7.6 Hz), 7.71 (1H, d, J=7.6 Hz), 8.04 (1H, d, J=16.0 Hz), 8.59 (1H, br s).

Workup

  1. temperatureAfter cooling to room temperature
  2. stirringthe mixture was stirred at 75° C. for 47 hours under a stream of nitrogen
  3. temperatureAfter cooling to room temperature
  4. stirringthe mixture was stirred at 100° C. for 95 hours under a stream of nitrogen
  5. temperatureAfter cooling to room temperature
  6. concentrationthe reaction mixture was concentrated under reduced pressure
  7. additionTo the obtained residue, a hexane/ethyl acetate mixed solution (1:1, 300 ml) was added
  8. washthe organic layer was washed with water
  9. extractionThe obtained aqueous layer was subjected to extraction with a hexane/ethyl acetate (1:1)
  10. additionmixed solution
  11. washthe combined organic layer was washed with saturated saline
  12. dry with materialThe obtained organic layer was dried over anhydrous magnesium sulfate
  13. concentrationconcentrated under reduced pressure
  14. customThe obtained residue was purified by silica gel chromatography (eluent; hexane:ethyl acetate=6:1)

Sources & evidence

ORD record
ord-d355fb25ef4b42a8b55df0ae0380cbc5
Source dataset
uspto-grants-2013_06
Patent number
US08470786B2

Reaction notes

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