Cesium carbonate → HCID 117749293, compound

HRID 1504527Notes

Reaction equation

HRID 1504527 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:4][C:3]=1/[CH:16]=[CH:17]/[C:18]([O:20][CH2:21][CH3:22])=[O:19].[Cl:23][C:24]1[CH:29]=[C:28](I)[C:27]([O:31][CH3:32])=[CH:26][C:25]=1[C:33]([F:36])([F:35])[F:34].C(=O)([O-])[O-].[Cs+].[Cs+]>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].CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:9]([S:8][C:5]1[CH:6]=[CH:7][C:2]([NH:1][C:28]2[CH:29]=[C:24]([Cl:23])[C:25]([C:33]([F:36])([F:34])[F:35])=[CH:26][C:27]=2[O:31][CH3:32])=[C:3](/[CH:16]=[CH:17]/[C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH:4]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 117736932HCID 117736932, compoundHCID 117740420(E)-Ethyl 3-(2-amino-5-(benzylthio)phenyl)acrylate

Product 1

HCID 117749293HCID 117749293, compoundYield 103%

Reagents, catalysts & solvents 2

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
100 °C

Procedure

A flask was charged with (E)-ethyl 3-(2-amino-5-(benzylthio)phenyl)acrylate (Bellen Chemistry Co., 3.2 g, 10.21 mmol), 1-chloro-5-iodo-4-methoxy-2-(trifluoromethyl)benzene (4.12 g, 12.25 mmol), cesium carbonate (4.66 g, 14.29 mmol), Pd2(dba)3 (0.234 g, 0.255 mmol), and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.295 g, 0.511 mmol) (XANTPHOS). The flask was flushed with nitrogen and a reflux condensor was added. CPME (20.42 mL) was added and the flask was heated to 100° C. with vigorous stirring. The reaction was stopped at 24 h and cooled to RT. Water and EtOAc were added (30 mL each), and the layers were separated. The aqueous layer was extracted again with EtOAc (50 mL). The combined organics were passed through a plug of Celite/silica to remove Pd, and the orange filtrate was concentrated. The residue was triturated with isopropanol, filtered through a medium glass frit, and the solid was dried under high vac to provide (E)-ethyl 3-(5-(benzylthio)-2-((5-chloro-2-methoxy-4-(trifluoromethyl)phenyl)amino)phenyl)acrylate (5.48 g, 10.50 mmol, 103% yield). m/z (ESI) 520.2 (M−H)−.

Workup

  1. customThe flask was flushed with nitrogen
  2. additiona reflux condensor was added
  3. additionCPME (20.42 mL) was added
  4. temperaturecooled to RT
  5. additionWater and EtOAc were added (30 mL each)
  6. customthe layers were separated
  7. extractionThe aqueous layer was extracted again with EtOAc (50 mL)
  8. customto remove Pd
  9. concentrationthe orange filtrate was concentrated
  10. customThe residue was triturated with isopropanol
  11. filtrationfiltered through a medium glass frit
  12. customthe solid was dried under high vac

Sources & evidence

ORD record
ord-aeb8d4c5414440969726b697a0af6777
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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