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

HRID 226358Notes

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].C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:22]([N:29]1[CH2:33][CH2:32][C@@H:31]([NH2:34])[CH2:30]1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:22]([N:29]1[CH2:33][CH2:32][C@@H:31]([NH:34][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])[CH2:30]1)[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1

Participants

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-diphenylamine (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

additionThe resulting mixture was poured
extractionNH4Cl aqueous solution and extracted with AcOEt
washThe organic layer was washed with sat. NH4Cl aq solution, water, and brine
dry with materialdried over Na2SO4
customThe solvent was removed in vacuo and residual brown oil
customwas purified by preparative thin layer chromatography (chloroform:methanol 90:10)

Sources & evidence

ORD record: ord-23080bb545eb42e198c46e9e7a4fb89d
Source dataset: uspto-grants-2009_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07557127B2

Reaction notes

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