Cesium carbonate → ethyl (2E)-3-(6-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}-5-methyl-3-pyridyl)acrylate

HRID 2376043Notes

Reaction equation

HRID 2376043 reaction equation
Br[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][C:3]=1[CH3:15].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(N(C)C)=CC=CC=2)CCCCC1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:50]([N:57]1[CH2:61][CH2:60][C@@H:59]([NH2:62])[CH2:58]1)[C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:50]([N:57]1[CH2:61][CH2:60][C@@H:59]([NH:62][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][C:3]=2[CH3:15])[CH2:58]1)[C:51]1[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 1519354(3R)-1-benzylpyrrolidin-3-amineHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 86603663ethyl (2E)-3-(6-bromo-5-methyl-3-pyridyl)acrylate

Product 1

HCID 86603664ethyl (2E)-3-(6-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}-5-methyl-3-pyridyl)acrylateYield 54.1%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

To a solution of ethyl (2E)-3-(6-bromo-5-methyl-3-pyridyl)acrylate (500 mg) in dioxane (5 mL) was added palladium(II) acetate (41.6 mg) and 2′-(dicyclohexylphosphino)-N,N-dimethyl-2-biphenylamine (109 mg) and cesium carbonate (843 mg), and (3R)-(−)-1-benzyl-3-aminopyrrolidine (359 mg). The mixture was heated at 100° C. for 18 hours. 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 preparative thin layer chromatography (chloroform:methanol=90:10) to give ethyl (2E)-3-(6-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}-5-methyl-3-pyridyl)acrylate (366 mg) as pale yellow oil.

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 preparative thin layer chromatography (chloroform:methanol=90:10)

Sources & evidence

ORD record
ord-5d0fd6d1002d4c9aa95830a640619ac1
Source dataset
uspto-grants-2008_12
Patent number
US07465731B2

Reaction notes

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