Cesium carbonate → HCID 117746874, compound

HRID 1504482Notes

Reaction equation

HRID 1504482 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].[Br:23][C:24]1[CH:29]=[C:28]([Cl:30])[CH:27]=[CH:26][C:25]=1I.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(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[CH2:9]([S:8][C:5]1[CH:6]=[CH:7][C:2]([NH:1][C:25]2[CH:26]=[CH:27][C:28]([Cl:30])=[CH:29][C:24]=2[Br:23])=[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 137413262-Bromo-4-chloro-1-iodobenzeneHCID 117740420(E)-Ethyl 3-(2-amino-5-(benzylthio)phenyl)acrylate

Product 1

HCID 117746874HCID 117746874, compoundYield 79.2%

Reagents, catalysts & solvents 2

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

Procedure

A RBF was charged with (E)-ethyl 3-(2-amino-5-(benzylthio)phenyl)acrylate (8.25 g, 26.3 mmol, made via Method 42, Steps 1-2), 2-bromo-4-chloro-1-iodobenzene (10.02 g, 31.6 mmol), Xantphos (0.762 g, 1.316 mmol), Pd2(dba)3 (0.603 g, 0.658 mmol), and cesium carbonate (21.44 g, 65.8 mmol) were added. A reflux condenser was attached and the flask was lowered into a 110° C. heating bath for 1 h. The mixture was cooled to room temperature then filtered through celite with the aid of toluene. The filtrate was concentrated. The residue was taken up in 2-PrOH and concentrated to give a yellow solid with some tan chunks. The mixture was taken up in 2-PrOH and the resulting slurry was heated to boiling for 5 min to give a brown solution (after breaking up some solid with a spatula). The resulting solution was allowed to cool to RT while being stirred. The mixture became a thick slurry that was diluted with 2-PrOH and filtered. The collected solid was washed with 2-PrOH (3×), then dried under a stream of N2 (g) to give (E)-ethyl 3-(5-(benzylthio)-2-((2-bromo-4-chlorophenyl)amino)phenyl)acrylate (10.473 g, 20.83 mmol, 79% yield) as a bright-yellow solid. 1 H NMR (400 MHz, DMSO-d6)□=7.76-7.61 (m, 4 H), 7.38-7.27 (m, 5 H), 7.27-7.20 (m, 2 H), 6.88 (d, J=8.4 Hz, 1 H), 6.62-6.52 (m, 2 H), 4.27 (s, 2 H), 4.14 (q, J=7.1 Hz, 2 H), 1.22 (t, J=7.1 Hz, 3 H). m/z (ESI) 502.0 (M+H)+.

Workup

  1. additionwere added
  2. customA reflux condenser was attached
  3. customwas lowered into a 110° C.
  4. temperatureheating bath for 1 h
  5. filtrationthen filtered through celite with the aid of toluene
  6. concentrationThe filtrate was concentrated
  7. concentrationconcentrated
  8. customto give a yellow solid with some tan chunks
  9. temperaturethe resulting slurry was heated
  10. customto give a brown solution (
  11. temperatureto cool to RT
  12. filtrationfiltered
  13. washThe collected solid was washed with 2-PrOH (3×)
  14. dry with materialdried under a stream of N2 (g)

Sources & evidence

ORD record
ord-a5825f9fed0f4d558d33325b6f29ef6c
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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