Potassium Fluoride → 4-(5-Formyl-2,4-dimethoxy-phenyl)-pyrazole-1-carboxylic acid tert-butyl ester

HRID 10695Notes

Reaction equation

HRID 10695 reaction equation
[CH3:1][O:2][C:3]1[CH:10]=[C:9]([O:11][CH3:12])[C:8](Br)=[CH:7][C:4]=1[CH:5]=[O:6].[C:14]([O:18][C:19]([N:21]1[CH:25]=[C:24](B2OC(C)(C)C(C)(C)O2)[CH:23]=[N:22]1)=[O:20])([CH3:17])([CH3:16])[CH3:15].[F-].[K+]>CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C.O>[C:14]([O:18][C:19]([N:21]1[CH:25]=[C:24]([C:8]2[CH:7]=[C:4]([CH:5]=[O:6])[C:3]([O:2][CH3:1])=[CH:10][C:9]=2[O:11][CH3:12])[CH:23]=[N:22]1)=[O:20])([CH3:17])([CH3:15])[CH3:16]

Participants

6

Reactant 3

HCID 522689Potassium Fluoride2×HCID 6683465-Bromo-2,4-dimethoxybenzaldehydeHCID 16217654tert-butyl 4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate

Product 1

HCID 879312344-(5-Formyl-2,4-dimethoxy-phenyl)-pyrazole-1-carboxylic acid tert-butyl esterYield 40%

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

Ex-74B: To a mixture of 2,4-dimethoxy-5-bromo-benzaldehye (0.28 g, 1.13 mmol), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrazole-1-carboxylic acid tert-butyl ester (Ex-76A, 0.61 g, 1.70 mmol), bis(tri-tert-butylphosphine)palladium (43 mg, 0.085 mmol) and potassium fluoride (0.24 g, 4.08 mmol) was added degassed tetrahydrofuran (15 mL). The reaction mixture was heated at 60° C. for one day. Additional potassium fluoride (0.24 g, 4.08 mmol) and water (20 μL) were added. The reaction mixture continued to stir at 60° C. for another 8 hours. The reaction was then quenched by water. The aqueous solution was extracted with ethyl acetate. The solution of ethyl acetate was washed with saturated solution of sodium bicarbonate, brine, dried over sodium sulfate and concentrated. The crude product was purified by flash chromatography. Elution with ethyl acetate (50%, v/v, in hexane) afforded 4-(5-formyl-2,4-dimethoxy-phenyl)-pyrazole-1-carboxylic acid tert-butyl ester (0.15 g, 40%) as white solid. 1H NMR (CDCl3) δ 10.35 (s, 1H), 8.43 (s, 1H), 8.09 (s, 1H), 8.02 (s, 1H), 6.52 (s, 1H), 4.02 (s, 3H), 3.99 (s, 3H), 1.68 (s, 9H). MS m/z=333 ([M+H]+, 100%).

Workup

  1. additionwas added
  2. customdegassed tetrahydrofuran (15 mL)
  3. customThe reaction was then quenched by water
  4. extractionThe aqueous solution was extracted with ethyl acetate
  5. washThe solution of ethyl acetate was washed with saturated solution of sodium bicarbonate, brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. customThe crude product was purified by flash chromatography
  9. washElution with ethyl acetate (50%, v/v, in hexane)

Sources & evidence

ORD record
ord-c5a59805c40043619e3eed95fb6c9b8a
Source dataset
uspto-grants-2006_08
Patent number
US07094801B2

Reaction notes

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