Cesium carbonate → methyl 5-(1H-pyrazol-4-yl)thiophene-3-carboxylate

HRID 1914571Notes

Reaction equation

HRID 1914571 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:9]=[C:8](Br)[S:7][CH:6]=1)=[O:4].C(OC([N:18]1[CH:22]=[C:21](B2OC(C)(C)C(C)(C)O2)[CH:20]=[N:19]1)=O)(C)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+]>COCCOC.O.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.[Pd]>[CH3:1][O:2][C:3]([C:5]1[CH:9]=[C:8]([C:21]2[CH:22]=[N:18][NH:19][CH:20]=2)[S:7][CH:6]=1)=[O:4]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 16217654tert-butyl 4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylateHCID 45873035Methyl 5-bromothiophene-3-carboxylate

Product 1

HCID 58110358methyl 5-(1H-pyrazol-4-yl)thiophene-3-carboxylate

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
140 °C

Procedure

5-Bromo-thiophene-3-carboxylic acid methyl ester (1.29 g, 5.84 mmol) was dissolved in DME (13.5 mL), IMS (4.5 mL) and water (2 mL) and), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrazole-1-carboxylic acid tert-butyl ester (1.89 g, 6.43 mmol) and caesium carbonate (2.85 g, 8.77 mmol) were added followed by palladium tetrakis(triphenylphosphine) (0.675 g, 5.84 mmol). The reaction mixture was heated by microwave irradiation at 140° C. for 20 minutes and then diluted with water and extracted with DCM (×3). The organic solution was dried over sodium sulfate, filtered and the solvent evaporated. The residue was purified by chromatography on a silica II cartridge, eluting with 10 to 50% ethyl acetate in cyclohexane. The fractions containing the desired product were concentrated under vacuum to give 5-(1H-pyrazol-4-yl)-thiophene-3-carboxylic acid methyl ester as a white, flocculent solid (0.728 g).

Workup

  1. extractionextracted with DCM (×3)
  2. dry with materialThe organic solution was dried over sodium sulfate
  3. filtrationfiltered
  4. customthe solvent evaporated
  5. customThe residue was purified by chromatography on a silica II cartridge
  6. washeluting with 10 to 50% ethyl acetate in cyclohexane
  7. additionThe fractions containing the desired product
  8. concentrationwere concentrated under vacuum

Sources & evidence

ORD record
ord-8cf1a2a38ce746a5af269fc89293546d
Source dataset
uspto-grants-2013_12
Patent number
US08614209B2

Reaction notes

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