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Cesium carbonate → (E)-ethyl 3-(5-(benzylthio)-2-((5-bromo-2-methoxyphenyl)amino)phenyl)acrylate

HRID 1504436
Notes
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Reaction equation

HRID 1504436 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[C:4](I)[CH:3]=1.[NH2:11][C:12]1[CH:17]=[CH:16][C:15]([S:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[CH:14][C:13]=1/[CH:26]=[CH:27]/[C:28]([O:30][CH2:31][CH3:32])=[O:29].C(=O)([O-])[O-].[Cs+].[Cs+]>COC1CCCC1.CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:19]([S:18][C:15]1[CH:16]=[CH:17][C:12]([NH:11][C:4]2[CH:3]=[C:2]([Br:1])[CH:7]=[CH:6][C:5]=2[O:8][CH3:9])=[C:13](/[CH:26]=[CH:27]/[C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH:14]=1)[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 109799044-Bromo-2-iodo-1-methoxybenzeneHCID 117740420(E)-Ethyl 3-(2-amino-5-(benzylthio)phenyl)acrylate

Product 1

HCID 117746858(E)-ethyl 3-(5-(benzylthio)-2-((5-bromo-2-methoxyphenyl)amino)phenyl)acrylateYield 86%

Reagents, catalysts & solvents 3

HCID 9811564
Bis(dibenzylideneacetone)palladium
Catalyst
HCID 8857Ethyl AcetateSolvent
HCID 138539Cyclopentyl methyl etherSolvent

Conditions

Temperature
90 °C

Procedure

4-Bromo-2-iodo-1-methoxybenzene (6.07 g, 19.40 mmol), (E)-ethyl 3-(2-amino-5-(benzylthio)phenyl)acrylate (5.066 g, 16.16 mmol), Pd2(dba)3 (0.370 g, 0.404 mmol), Xntphos (0.468 g, 0.808 mmol) and cesium carbonate (7.37 g, 22.63 mmol) were combined in CPME (32.3 ml) and the reaction was heated to 90° C. overnight. The reaction was cooled to RT, diluted with EtOAc and filtered over a pad of Celite (washing with EtOAc). The filtrate was concentrated in vacuo and the crude oil was then taken up in DCM and purified via MPLC, eluting with 0-20% ethyl acetate in heptanes to yield (E)-ethyl 3-(5-(benzylthio)-2-((5-bromo-2-methoxyphenyl)amino)phenyl)acrylate (6.92 g, 13.88 mmol, 86% yield) as a yellow solid. MS (ESI, pos. ion) m/z: [M+1] 498.0

Workup

  1. temperatureThe reaction was cooled to RT
  2. filtrationfiltered over a pad of Celite (washing with EtOAc)
  3. concentrationThe filtrate was concentrated in vacuo
  4. custompurified via MPLC
  5. washeluting with 0-20% ethyl acetate in heptanes

Sources & evidence

ORD record
ord-c65dc5b665e646028d9ccb183b65b935
Source dataset
uspto-grants-2015_12
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09212182B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes