Cesium carbonate → HCID 117746866, compound

HRID 1504465Notes

Reaction equation

HRID 1504465 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]([O:30][CH3:31])[C:27](I)=[CH:26][C:25]=1[CH3:33].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.C1(C)C=CC=CC=1>[CH2:9]([S:8][C:5]1[CH:6]=[CH:7][C:2]([NH:1][C:27]2[CH:26]=[C:25]([CH3:33])[C:24]([Br:23])=[CH:29][C:28]=2[O:30][CH3:31])=[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 509981771-Bromo-4-iodo-5-methoxy-2-methylbenzene2×HCID 117740420(E)-Ethyl 3-(2-amino-5-(benzylthio)phenyl)acrylate

Product 1

HCID 117746866HCID 117746866, compoundYield 67.4%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)Catalyst2×HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 1140TolueneSolvent

Procedure

A RBF was charged with (E)-ethyl 3-(2-amino-5-(benzylthio)phenyl)acrylate (4.729 g, 15.09 mmol, made via Method 42, Steps 1-2), 1-bromo-4-iodo-5-methoxy-2-methylbenzene (5.18 g, 15.84 mmol, Oakwood), Xantphos (0.437 g, 0.754 mmol), Pd2(dba)3 (0.345 g, 0.377 mmol), cesium carbonate (9.83 g, 30.2 mmol), and toluene (30 mL) were added. A reflux condenser was attached, and the mixture was heated to reflux. After 4 h, additional portions of Pd2(dba)3 (172 mg) and Xantphos (213 mg) were added. After 2 h, additional portions of cesium carbonate (ca. 2 g) and 1-bromo-4-iodo-5-methoxy-2-methylbenzene (600 mg) were added. Following an additional 30 min of reflux, mixture was cooled and filtered through celite. The filter pad was washed with EtOAc (3×). The filtrate was concentrated. The residue was concentrated from MeOH, and taken up in MeOH. The resulting suspension was heated to boiling, then sonicated and cooled to RT. The mixture was filtered, and the collected solid was washed with MeOH (3×) and dried under a stream of N2 (g) for 48 hrs to give (E)-ethyl 3-(5-(benzylthio)-2-((4-bromo-2-methoxy-5-methylphenyl)amino)phenyl)acrylate (5.21 g, 10.17 mmol, 67.4% yield) as a bright-yellow solid. 1H NMR (400 MHz, DMSO-d6) □=7.75 (d, J=15.9 Hz, 1 H), 7.66 (d, J=2.1 Hz, 1H), 7.42 (s, 1 H), 7.37-7.20 (m, 6 H), 7.14 (s, 1 H), 6.85 (d, J=8.5 Hz, 1 H), 6.62 (s, 1 H), 6.51 (d, J=15.9 Hz, 1 H), 4.23 (s, 2 H), 4.15 (q, J=7.0 Hz, 2 H), 3.78 (s, 3 H), 2.14 (s, 2 H), 1.23 (t, J=7.1 Hz, 3 H). m/z (ESI) 512.2 (M+H)+.

Workup

  1. additionwere added
  2. customA reflux condenser was attached
  3. temperaturethe mixture was heated to reflux
  4. waitAfter 2 h
  5. waitFollowing an additional 30 min
  6. temperatureof reflux
  7. temperaturemixture was cooled
  8. filtrationfiltered through celite
  9. washThe filter pad was washed with EtOAc (3×)
  10. concentrationThe filtrate was concentrated
  11. concentrationThe residue was concentrated from MeOH
  12. temperatureThe resulting suspension was heated
  13. customsonicated
  14. filtrationThe mixture was filtered
  15. washthe collected solid was washed with MeOH (3×)
  16. dry with materialdried under a stream of N2 (g) for 48 hrs

Sources & evidence

ORD record
ord-3015bdaa247c459eb747f8b42ee2c661
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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