Sodium Carbonate → ethyl 1-(1-ethoxyethyl)-3-((E)-styryl)-1H-thieno[2,3-c]pyrazole-5-carboxylate

HRID 1363071Notes

Reaction equation

HRID 1363071 reaction equation
[CH:1](/B(O)O)=[CH:2]\[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C(=O)([O-])[O-].[Na+].[Na+].Br[C:19]1[C:20]2[CH:31]=[C:30]([C:32]([O:34][CH2:35][CH3:36])=[O:33])[S:29][C:21]=2[N:22]([CH:24]([O:26][CH2:27][CH3:28])[CH3:25])[N:23]=1>C(O)C.O.C1(C)C=CC=CC=1.C(OCC)(=O)C.[Pd].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.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>[CH2:27]([O:26][CH:24]([N:22]1[C:21]2[S:29][C:30]([C:32]([O:34][CH2:35][CH3:36])=[O:33])=[CH:31][C:20]=2[C:19](/[CH:1]=[CH:2]/[C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=2)=[N:23]1)[CH3:25])[CH3:28]

Participants

9

Reactant 3

HCID 10340Sodium CarbonateHCID 5702628Styrylboronic acidHCID 57487832ethyl 3-bromo-1-(1-ethoxyethyl)-1H-thieno[2,3-c]pyrazole-5-carboxylate

Product 1

HCID 57487834ethyl 1-(1-ethoxyethyl)-3-((E)-styryl)-1H-thieno[2,3-c]pyrazole-5-carboxylateYield 87.2%

Reagents, catalysts & solvents 5

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
82 °C

Procedure

1.7 g (1.4 mmol) of tetrakis(triphenylphosphine)-palladium [0], a solution of 6.6 g (43.2 mmol) of trans-β-styreneboronic acid in 40 cm3 of ethanol, and then a solution of 9.2 g (86.4 mmol) of sodium carbonate in 40 cm3 of water are successively added to a solution of 10.0 g (28.8 mmol) of ethyl 3-bromo-1-(1-ethoxyethyl)-1H-thieno[2,3-c]pyrazole-5-carboxylate in 300 cm3 of toluene. The reaction mixture is heated at a temperature in the region of 82° C. for 2.5 hours and is then cooled to a temperature in the region of 25° C. and diluted with 500 cm3 of water and 300 cm3 of ethyl acetate. After separation of the phases by settling, the organic phase is washed successively with twice 300 cm3 of water and then 300 cm3 of saturated brine. The organic phase is then dried over magnesium sulfate, filtered and then concentrated to dryness under reduced pressure (2.7 kPa) at a temperature in the region of 40° C. The residue is purified by chromatography under a pressure of argon (80 kPa), on a cartridge containing 330 g of silica gel (particle size 32-63 μm), eluting with a cyclohexane/ethyl acetate mixture (90/10 by volume). The fractions containing the expected product are combined and concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. 9.3 g of ethyl 1-(1-ethoxyethyl)-3-((E)-styryl)-1H-thieno[2,3-c]pyrazole-5-carboxylate are thus obtained in the form of a yellow solid. (Rf=0.70, thin-layer chromatography on silica gel, eluent: dichloromethane/methanol (98/2 by volume)).

Workup

  1. temperatureis then cooled to a temperature in the region of 25° C.
  2. customAfter separation of the phases
  3. washthe organic phase is washed successively with twice 300 cm3 of water
  4. dry with materialThe organic phase is then dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to dryness under reduced pressure (2.7 kPa) at a temperature in the region of 40° C
  7. customThe residue is purified by chromatography under a pressure of argon (80 kPa), on a cartridge
  8. additioncontaining 330 g of silica gel (particle size 32-63 μm)
  9. washeluting with a cyclohexane/ethyl acetate mixture (90/10 by volume)
  10. additionThe fractions containing the expected product
  11. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C

Sources & evidence

ORD record
ord-4db052871a664e6fac0fac344b15d385
Source dataset
uspto-grants-2011_02
Patent number
US07884123B2

Reaction notes

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