Cesium carbonate → (E)-ethyl 3-(5-(benzylthio)-2-((4-bromo-2-methoxyphenyl)amino)phenyl)acrylate

HRID 1504472Notes

Reaction equation

HRID 1504472 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]=[CH:28][C:27](I)=[C:26]([O:31][CH3:32])[CH:25]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>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].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:27]2[CH:28]=[CH:29][C:24]([Br:23])=[CH:25][C:26]=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

7

Reactant 3

HCID 10796Cesium carbonate2×HCID 468357314-Bromo-1-iodo-2-methoxybenzeneHCID 117740420(E)-Ethyl 3-(2-amino-5-(benzylthio)phenyl)acrylate

Product 1

HCID 117746872(E)-ethyl 3-(5-(benzylthio)-2-((4-bromo-2-methoxyphenyl)amino)phenyl)acrylateYield 83%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

A RBF was charged with (E)-ethyl 3-(2-amino-5-(benzylthio)phenyl)acrylate (2.39 g, 7.63 mmol, made via Method 42, Steps 1-2), 4-bromo-1-iodo-2-methoxybenzene (2.86 g, 9.15 mmol), Xantphos (0.221 g, 0.381 mmol), Pd2(dba)3 (0.175 g, 0.191 mmol), and cesium carbonate (4.97 g, 15.25 mmol) were added. A reflux condenser was attached and the flask was lowered into a 110° C. heating bath. After 2 h, an additional portion of cesium carbonate (1.4 g) was added, and the bath temperature was raised to 120° C. The mixture was heated for another 2 h then cooled to room temperature, diluted with EtOAc, and filtered through celite with the aid of EtOAc. The filtrate was concentrated. The oily residue was taken up in 2-PrOH. The mixture was concentrated to give a yellow solid with some oily solid present. The mixture was taken up in 2-PrOH to give a suspension, and the suspension was stirred for 16 hrs. The mixture was filtered, and the filtered solid was washed with 2-PrOH (3×). The collected solid was dried on the filter under a flow of N2 (g) for 15 min to give (E)-ethyl 3-(5-(benzylthio)-2-((4-bromo-2-methoxyphenyl)amino)phenyl)acrylate (3.136 g, 6.29 mmol, 83% yield) as a bright-yellow solid. 1 H NMR (400 MHz, DMSO-d6) □=7.72 (d, J=16.0 Hz, 1H), 7.68 (d, J=2.2 Hz, 1 H), 7.47 (s, 1 H), 7.37-7.19 (m, 6 H), 7.13 (d, J=2.2 Hz, 1 H), 6.94 (dd, J=2.2, 8.4 Hz, 1 H), 6.86 (d, J=8.5 Hz, 1 H), 6.55 (s, 1 H), 6.52 (d, J=7.7 Hz, 1H), 4.24 (s, 2 H), 4.15 (q, J=7.1 Hz, 2 H), 3.82 (s, 3 H), 1.23 (t, J=7.1 Hz, 3 H). m/z (ESI) 498.0 (M+H)+.

Workup

  1. additionwere added
  2. customA reflux condenser was attached
  3. customwas lowered into a 110° C.
  4. temperatureheating bath
  5. temperatureThe mixture was heated for another 2 h
  6. temperaturethen cooled to room temperature
  7. filtrationfiltered through celite with the aid of EtOAc
  8. concentrationThe filtrate was concentrated
  9. concentrationThe mixture was concentrated
  10. customto give a yellow solid with some oily solid present
  11. customto give a suspension
  12. filtrationThe mixture was filtered
  13. washthe filtered solid was washed with 2-PrOH (3×)
  14. customThe collected solid was dried on the
  15. filtrationfilter under a flow of N2 (g) for 15 min

Sources & evidence

ORD record
ord-3242ffceaf5f452aaee1440e297417d2
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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