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Cesium carbonate → ethyl (2E)-3-(6-{[(3R)-1-(4-chlorobenzoyl)-3-pyrrolidinyl]amino}-3-pyridyl)acrylate

HRID 2376034
Notes
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Reaction equation

HRID 2376034 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.C(=O)([O-])[O-].[Cs+].[Cs+].[Cl:21][C:22]1[CH:35]=[CH:34][C:25]([C:26]([N:28]2[CH2:32][CH2:31][C@@H:30]([NH2:33])[CH2:29]2)=[O:27])=[CH:24][CH:23]=1>O1CCOCC1.CCOC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(N(C)C)=CC=CC=2)CCCCC1>[Cl:21][C:22]1[CH:35]=[CH:34][C:25]([C:26]([N:28]2[CH2:32][CH2:31][C@@H:30]([NH:33][C:2]3[N:7]=[CH:6][C:5](/[CH:8]=[CH:9]/[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:4][CH:3]=3)[CH2:29]2)=[O:27])=[CH:24][CH:23]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 3

HCID 10796Cesium carbonateHCID 108461873-(6-Chloro-pyridin-3-yl)-acrylic acid ethyl esterHCID 68963176(3R)-1-(4-chlorobenzoyl)-3-pyrrolidinamine

Product 1

HCID 86603659ethyl (2E)-3-(6-{[(3R)-1-(4-chlorobenzoyl)-3-pyrrolidinyl]amino}-3-pyridyl)acrylateYield 32.7%

Reagents, catalysts & solvents 4

HCID 167845
palladium(II) acetate
Catalyst
HCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylCatalyst
HCID 8857Ethyl AcetateSolvent
HCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of ethyl (2E)-3-(6-chloro-3-pyridyl)acrylate (3.5 g) in dioxane (70 mL) was added palladium(II) acetate (371 mg) and 2′-(dicyclohexylphosphino)-N,N-dimethyl-2-biphenylamine (110 mg) and cesium carbonate (583 mg), and (3R)-1-(4-chlorobenzoyl)-3-pyrrolidinamine (4.09 g). The mixture was heated at 90° C. for 3 hours. The resulting mixture was diluted with AcOEt, and the precipitate was removed by filtration. The filtrate was concentrated and residual brown oil was purified by purified by silica gel column chromatography eluted with AcOEt and hexane (1:4)-AcOEt to give ethyl (2E)-3-(6-{[(3R)-1-(4-chlorobenzoyl)-3-pyrrolidinyl]amino}-3-pyridyl)acrylate (2.16 g) as dark yellow form.

Workup

  1. customthe precipitate was removed by filtration
  2. concentrationThe filtrate was concentrated
  3. customresidual brown oil was purified
  4. customby purified by silica gel column chromatography
  5. washeluted with AcOEt and hexane (1:4)-AcOEt

Sources & evidence

ORD record
ord-095b240c2a4d4283ac372fc039136bbf
Source dataset
uspto-grants-2008_12
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07465731B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes