Cesium carbonate → ethyl (2E)-3-(6-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}-3-pyridyl)acrylate

HRID 2376028Notes

Reaction equation

HRID 2376028 reaction equation
Cl[C:2]1[N: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>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[N: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

7

Reactant 4

HCID 10796Cesium carbonateHCID 1519354(3R)-1-benzylpyrrolidin-3-amineHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 108461873-(6-Chloro-pyridin-3-yl)-acrylic acid ethyl ester

Product 1

HCID 86603619ethyl (2E)-3-(6-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}-3-pyridyl)acrylateYield 45.1%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
95 °C

Procedure

To a solution of ethyl (2E)-3-(6-chloro-3-pyridyl)acrylate (14.3 g) in dioxane (140 mL) was added palladium(II) acetate (1.52 g), 2′-(dicyclohexylphosphino)-N,N-dimethyl-2-biphenylamine (3.99 g), cesium carbonate (30.2 g), and (3R)-(−)-1-benzyl-3-aminopyrrolidine (13.1 g), and the mixture was heated at 95° C. for 2.5 days. The resulting mixture was poured into sat.NH4Cl aqueous 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 AcOEt to give ethyl (2E)-3-(6-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}-3-pyridyl)acrylate as pale yellow oil (10.7 g)

Workup

  1. additionThe resulting mixture was poured
  2. extractionNH4Cl aqueous solution and extracted with AcOEt
  3. washThe organic layer was washed with sat. NH4Cl aq solution, water, and brine
  4. dry with materialdried over Na2SO4
  5. customThe solvent was removed in vacuo and residual brown oil
  6. customwas purified by silica gel column chromatography
  7. washeluted with AcOEt

Sources & evidence

ORD record
ord-343672d13e874fa28565a7a7d0868aa8
Source dataset
uspto-grants-2008_12
Patent number
US07465731B2

Reaction notes

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