Ethyl Acrylate → 5-(4-Fluorophenyl)-3-(1-methylethyl)-1-(2-pyrimidinyl)-1H-pyrazole 2-propenoic acid, ethyl ester

HRID 1032452Notes

Reaction equation

HRID 1032452 reaction equation
[C:1]([O:5][CH2:6][CH3:7])(=[O:4])[CH:2]=[CH2:3].Br[C:9]1[C:10]([CH:27]([CH3:29])[CH3:28])=[N:11][N:12]([C:21]2[N:26]=[CH:25][CH:24]=[CH:23][N:22]=2)[C:13]=1[C:14]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=1>CN(C=O)C.CCN(CC)CC.CCOCC.O.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:20][C:17]1[CH:18]=[CH:19][C:14]([C:13]2[N:12]([C:21]3[N:26]=[CH:25][CH:24]=[CH:23][N:22]=3)[N:11]=[C:10]([CH:27]([CH3:29])[CH3:28])[CH:9]=2)=[CH:15][CH:16]=1.[C:1]([O:5][CH2:6][CH3:7])(=[O:4])[CH:2]=[CH2:3]

Participants

8

Reactant 2

HCID 8821Ethyl AcrylateHCID 148513232-[4-bromo-5-(4-fluorophenyl)-3-(1-methylethyl)-1H-pyrazol-1-yl]pyrimidine

Product 1

HCID 867442225-(4-Fluorophenyl)-3-(1-methylethyl)-1-(2-pyrimidinyl)-1H-pyrazole 2-propenoic acid, ethyl ester

Reagents, catalysts & solvents 5

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

Ethyl acrylate (16.2 ml, 0.15 mol) and bis-(triphenylphosphine) palladium (II) chloride (0.84 g, 0.0012 mol) in DMF (75 ml) and Et3N (75 ml) was heated together at reflux under N2 with stirring until a homogeneous solution resulted. 2-[4-Bromo-5-(4-fluorophenyl))-3-(1-methylethyl)-1H-pyrazol-1-yl]pyrimidine (3) (10.8 g, 0.03 mol) was added and the resulting solution was heated at reflux for 24 hours, during which, an additional 1 mol % of catalyst was added. The mixture was then cooled to room temperature and diluted with ether and water. The organic layer was separated and washed with water and brine, dried over MgSO4, filtered and concentrated in vacuo. The resulting solid (10.4 g) was recrystallized from hexane/ethyl acetate, mp 155°-162° C.

Workup

  1. temperatureat reflux under N2
  2. customresulted
  3. temperaturethe resulting solution was heated
  4. temperatureat reflux for 24 hours, during which
  5. additionan additional 1 mol % of catalyst was added
  6. customThe organic layer was separated
  7. washwashed with water and brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe resulting solid (10.4 g) was recrystallized from hexane/ethyl acetate, mp 155°-162° C.

Sources & evidence

ORD record
ord-599e09fcfe9f4ea09233983333bc5570
Source dataset
uspto-grants-1990_09
Patent number
US04957971

Reaction notes

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