Potassium Fluoride → 4-methyl-3-[4-(3-methyl-3H-imidazol-4-yl)-pyrazol-1-yl]-benzoic acid ethyl ester

HRID 491852Notes

Reaction equation

HRID 491852 reaction equation
[CH2:1]([O:3][C:4](=[O:18])[C:5]1[CH:10]=[CH:9][C:8]([CH3:11])=[C:7]([N:12]2[CH:16]=[C:15](Br)[CH:14]=[N:13]2)[CH:6]=1)[CH3:2].[CH3:19][N:20]1[C:24]([Sn](CCCC)(CCCC)CCCC)=[CH:23][N:22]=[CH:21]1.[F-].[K+]>O1CCOCC1.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([O:3][C:4](=[O:18])[C:5]1[CH:10]=[CH:9][C:8]([CH3:11])=[C:7]([N:12]2[CH:16]=[C:15]([C:24]3[N:20]([CH3:19])[CH:21]=[N:22][CH:23]=3)[CH:14]=[N:13]2)[CH:6]=1)[CH3:2]

Participants

7

Reactant 3

HCID 522689Potassium FluorideHCID 109156511-Methyl-5-(tri-n-butylstannyl)imidazoleHCID 588614423-(4-Bromo-pyrazol-1-yl)-4-methyl-benzoic acid ethyl ester

Product 1

HCID 588612804-methyl-3-[4-(3-methyl-3H-imidazol-4-yl)-pyrazol-1-yl]-benzoic acid ethyl esterYield 26.5%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
100 °C

Procedure

3-(4-Bromo-pyrazol-1-yl)-4-methyl-benzoic acid ethyl ester (Example 8) (366 mg, 1.18 mmol) was dissolved in dioxane (2 mL) and flushed with nitrogen. 1-Methyl-5-tributylstannanyl-1H-imidazole (366 mg, 0.986 mmol) was added to the reaction flask in dioxane (0.5 mL) then the flask was purged with N2. After Pd(PPh3)4 (85 mg, 0.074 mmol) was added, the reaction was heated to 100° C. in a sealed tube. The reaction mixture was stirred with a 10% KF solution for 30 min then diluted with EtOAc. The layers were separated and the aqueous layer extracted with EtOAc (3×). The organic layers were combined, dried over Na2SO4, and concentrated. The resulting residue was purified by chromatography on silica gel (5% MeOH/CH2Cl2) to give the title compound (81 mg, 22%) as a colorless oil.

Workup

  1. customflushed with nitrogen
  2. customthe flask was purged with N2
  3. customThe layers were separated
  4. extractionthe aqueous layer extracted with EtOAc (3×)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customThe resulting residue was purified by chromatography on silica gel (5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-35e0271abd374558a43a1a9882a4d669
Source dataset
uspto-grants-2009_05
Patent number
US07531560B2

Reaction notes

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