Cesium carbonate → ethyl (2E)-3-(4-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}phenyl)acrylate

HRID 2376037Notes

Reaction equation

HRID 2376037 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5](/[CH:8]=[CH:9]/[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:4][CH:3]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(N(C)C)=CC=CC=2)CCCCC1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:49]([N:56]1[CH2:60][CH2:59][C@@H:58]([NH2:61])[CH2:57]1)[C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1.[NH4+].[Cl-]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:49]([N:56]1[CH2:60][CH2:59][C@@H:58]([NH:61][C:2]2[CH:7]=[CH:6][C:5](/[CH:8]=[CH:9]/[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:4][CH:3]=2)[CH2:57]1)[C:50]1[CH:51]=[CH:52][CH:53]=[CH:54][CH:55]=1

Participants

8

Reactant 5

HCID 10796Cesium carbonateHCID 25517Ammonium ChlorideHCID 688115Ethyl trans-4-BromocinnamateHCID 1519354(3R)-1-benzylpyrrolidin-3-amineHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenyl

Product 1

HCID 86603661ethyl (2E)-3-(4-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}phenyl)acrylateYield 74%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a solution of ethyl (2E)-3-(4-bromophenyl)acrylate (1.0 g) in dioxane (70 mL) was added palladium(II) acetate (88 mg), 2′-(dicyclohexylphosphino)-N,N-dimethyl-2-biphenylamine (231 mg), cesium carbonate (1.79 g), and (3R)-1-benzyl-3-pyrrolidinamine (760 mg). The mixture was heated at 90 for 24 hours. The resulting mixture was poured into sat NH4Cl aq solution and extracted with AcOEt. The organic layer was washed with sat. NH4Cl aq solution, water, and brine, and dried over Na2SO4. The solvent was removed in vacuo and residual brown oil was purified by silica gel column chromatography eluted with chloroform:methanol=9:1 to give ethyl (2E)-3-(4-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}phenyl)acrylate (1.017 g) as pale yellow oil.

Workup

  1. temperatureThe mixture was heated at 90 for 24 hours
  2. additionThe resulting mixture was poured
  3. extractionextracted with AcOEt
  4. washThe organic layer was washed with sat. NH4Cl aq solution, water, and brine
  5. dry with materialdried over Na2SO4
  6. customThe solvent was removed in vacuo and residual brown oil
  7. customwas purified by silica gel column chromatography
  8. washeluted with chloroform

Sources & evidence

ORD record
ord-2a11d577a22d4c919e8176a06f6fef95
Source dataset
uspto-grants-2008_12
Patent number
US07465731B2

Reaction notes

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