Methyl Acrylate → (E)-3-(4-{1-[2-(2-Methyl-1H-indol-3-yl)-ethyl]-pyrrolidin-2-yl}-phenyl)-acrylic acid methyl ester

HRID 549378Notes

Reaction equation

HRID 549378 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:12][CH2:11][CH2:10][N:9]2[CH2:13][CH2:14][C:15]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[NH:17][C:16]=2[CH3:24])=[CH:4][CH:3]=1.[C:25]([O:29][CH3:30])(=[O:28])[CH:26]=[CH2:27].N(C)(C1CCCCC1)C1CCCCC1>O1CCOCC1.C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:30][O:29][C:25](=[O:28])/[CH:26]=[CH:27]/[C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:12][CH2:11][CH2:10][N:9]2[CH2:13][CH2:14][C:15]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[NH:17][C:16]=2[CH3:24])=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 7294Methyl AcrylateHCID 24210N-Methyl dicyclohexylamineHCID 461979023-{2-[2-(4-bromophenyl)pyrrolidin-1-yl]ethyl}-2-methyl-1H-indole

Product 1

HCID 46197903(E)-3-(4-{1-[2-(2-Methyl-1H-indol-3-yl)-ethyl]-pyrrolidin-2-yl}-phenyl)-acrylic acid methyl esterYield 63.2%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of 3-{2-[2-(4-bromo-phenyl)-pyrrolidin-1-yl]-ethyl}-2-methyl-1H-indole (630 mg, 1.63 mmol), methyl acrylate (286 mg, 3.26 mmol), Pd2(dba)3 (14.9 mg, 0.0162 mmol), P(t-Bu)3HBF4 (18.9 mg, 0.0652 mmol) and Cy2NMe (414 μL, 1.95 mmol) in dioxane (10 mL) was heated at 100° C. by microwave for 60 minutes. The mixture was diluted with ethyl acetate, washed with water and brine, dried over magnesium sulfate, filtered, and concentrated to provide a crude product, which was purified on silica gel column chromatography to give (E)-3-(4-{1-[2-(2-Methyl-1H-indol-3-yl)-ethyl]-pyrrolidin-2-yl}-phenyl)-acrylic acid methyl ester (400 mg, 63%). LCMS (m/z): 388.97 (M+1).

Workup

  1. washwashed with water and brine
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto provide a crude product, which
  6. customwas purified on silica gel column chromatography

Sources & evidence

ORD record
ord-98b0c7c4e5b14bfdbec6f4411f02382d
Source dataset
uspto-grants-2011_05
Patent number
US07943652B2

Reaction notes

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