Cesium carbonate → 2-Methyl-2-(3-phenylethynyl-pyrazin-2-yl)-propionic acid ethyl ester

HRID 1852895Notes

Reaction equation

HRID 1852895 reaction equation
[CH2:1]([O:3][C:4](=[O:15])[C:5]([C:8]1[C:13](Cl)=[N:12][CH:11]=[CH:10][N:9]=1)([CH3:7])[CH3:6])[CH3:2].[C:16]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1C(F)(F)F)#[CH:17].C(=O)([O-])[O-].[Cs+].[Cs+]>C(#N)C>[CH2:1]([O:3][C:4](=[O:15])[C:5]([CH3:7])([C:8]1[C:13]([C:17]#[C:16][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[N:12][CH:11]=[CH:10][N:9]=1)[CH3:6])[CH3:2]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 41008561-Ethynyl-2-(trifluoromethyl)benzeneHCID 867018462-(3-Chloro-pyrazin-2-yl)-2-methyl-propionic acid ethyl ester

Product 1

HCID 690841742-Methyl-2-(3-phenylethynyl-pyrazin-2-yl)-propionic acid ethyl esterYield 57.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 2-(3-Chloro-pyrazin-2-yl)-2-methyl-propionic acid ethyl ester (0.70 g) in acetonitrile (7.0 ml) was added 1-ethynyl-2-trifluoromethylbenzene (0.781 g) and caesium carbonate (“Cs2CO3”) (2.99 g) and nitrogen bubbled through the solution for 20 min. To this solution was added as 4,5-(bisdiphenylphosphino)-9,9-dimethylxanthene (“Xantphos”) (0.133 g) and (1,1′-bis(diphenylphosphino)-ferrocene)dichloro palladium(2) (0.125 g) and the reaction mixture heated to reflux for 30 min. The reaction mixture was cooled to ambient temperature then filtered and concentrated. The residue was purified by chromatography on silica gel (eluent 5-95% ethyl acetate in isohexane) to give 2-methyl-2-(3-phenylethynyl-pyrazin-2-yl)-propionic acid ethyl ester (compound B1 of Table B) (0.52 g).

Workup

  1. custombubbled through the solution for 20 min
  2. additionTo this solution was added as 4,5-(bisdiphenylphosphino)-9,9-dimethylxanthene (“Xantphos”) (0.133 g) and (1,1′-bis(diphenylphosphino)-ferrocene)dichloro palladium(2) (0.125 g)
  3. temperaturethe reaction mixture heated
  4. temperatureto reflux for 30 min
  5. filtrationthen filtered
  6. concentrationconcentrated
  7. customThe residue was purified by chromatography on silica gel (eluent 5-95% ethyl acetate in isohexane)

Sources & evidence

ORD record
ord-0b7f9ef677dc4c849aeed9a18145354a
Source dataset
uspto-grants-2015_02
Patent number
US08962628B2

Reaction notes

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