Sodium Carbonate → Ethyl 3-(2,4-difluorophenyl)-1-(4-methoxybenzyl)-1H-thieno[2,3-c]pyrazole-5-carboxylate

HRID 1047615Notes

Reaction equation

HRID 1047615 reaction equation
Br[C:2]1[C:3]2[CH:18]=[C:17]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[S:16][C:4]=2[N:5]([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=2)[N:6]=1.[F:24][C:25]1[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:26]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:24][C:25]1[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:26]=1[C:2]1[C:3]2[CH:18]=[C:17]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[S:16][C:4]=2[N:5]([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=2)[N:6]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 10796Cesium carbonateHCID 27343342,4-Difluorophenylboronic acidHCID 66661729Ethyl 3-bromo-1-(4-methoxybenzyl)-1H-thieno[2,3-c]pyrazole-5-carboxylate

Product 1

HCID 66661061Ethyl 3-(2,4-difluorophenyl)-1-(4-methoxybenzyl)-1H-thieno[2,3-c]pyrazole-5-carboxylateYield 82%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Ethyl 3-bromo-1-(4-methoxybenzyl)-1H-thieno[2,3-c]pyrazole-5-carboxylate (1.1422 g, 2.89 mmol), 2,4-difluorophenylboronic acid (1.867 g, 11.82 mmol), sodium carbonate (1.614 g, 15.23 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.426 g, 0.582 mmol) were dissolved in dioxane (14.45 ml) at 25° C. under Ar in a sealed heavy-walled reaction vessel. The reaction mixture was heated to 80° C. and allowed to stir for 2 h. Cesium carbonate (1.52 g, 4.67 mmol) was added. The reaction was allowed to stir for 2 h. The reaction was stopped, cooled to room temperature, quenched by addition of saturated aqueous ammonium chloride (20 mL), and the mixture extracted with ethyl acetate (3×20 mL). The combined organic phases were washed with saturated aqueous sodium chloride (1×15 mL), dried (sodium sulfate), filtered, and the solvent evaporated under reduced pressure. The crude product was purified by flash chromatography (RediSep SiO2, 120 g column) on a CombiFlash purification system eluting with ethyl acetate-hexanes (0-15%). The title compound (1.0147 g, 2.368 mmol, 82% yield) was recovered as a white solid. LC-MS [M+1]=429.3

Workup

  1. stirringto stir for 2 h
  2. temperaturecooled to room temperature
  3. customquenched by addition of saturated aqueous ammonium chloride (20 mL)
  4. extractionthe mixture extracted with ethyl acetate (3×20 mL)
  5. washThe combined organic phases were washed with saturated aqueous sodium chloride (1×15 mL)
  6. dry with materialdried (sodium sulfate)
  7. filtrationfiltered
  8. customthe solvent evaporated under reduced pressure
  9. customThe crude product was purified by flash chromatography (RediSep SiO2, 120 g column) on a CombiFlash purification system
  10. washeluting with ethyl acetate-hexanes (0-15%)

Sources & evidence

ORD record
ord-f79478b32cb9443eb7a7441d09006cae
Source dataset
uspto-grants-2013_10
Patent number
US08569512B2

Reaction notes

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