Dichloromethane → Methyl 4-methyl-3-(1H-pyrazol-5-yl)benzoate

HRID 1487911Notes

Reaction equation

HRID 1487911 reaction equation
[CH3:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1B1OC(C)(C)C(C)(C)O1.I[C:22]1[NH:26][N:25]=[CH:24][CH:23]=1.C(Cl)Cl>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]>[CH3:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[C:22]1[NH:26][N:25]=[CH:24][CH:23]=1

Participants

6

Reactant 3

HCID 6344DichloromethaneHCID 12398303-Iodo-1H-pyrazoleHCID 532171365-Methoxycarbonyl-2-methylphenylboronic acid pinacol ester2×

Product 1

HCID 90030661Methyl 4-methyl-3-(1H-pyrazol-5-yl)benzoateYield 41.1%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
90 °C

Procedure

To methyl 4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (compound 5.4, 800 mg, 2.9 mmol) in dioxane (30 mL) was added 5-iodo-1H-pyrazole (674 mg, 3.5 mmol), and Pd(dppf)Cl2.DCM (237 mg, 0.29 mmol). The mixture was degassed with argon and stirred for 10 minutes then an aqueous potassium carbonate solution (2 M, 8 mL) was added. The mixture was heated at 90° C. for 18 h, then cooled and diluted with EtOAc and filtered through Celite®. The filtrate was washed with brine, dried (MgSO4), filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography (SiO2; 0-30% EtOAc in hexanes) to yield 258 mg (41%) of the title compound as a solid. m/z (ES+) 217 (M+H)+.

Workup

  1. customThe mixture was degassed with argon
  2. additionan aqueous potassium carbonate solution (2 M, 8 mL) was added
  3. temperaturecooled
  4. additiondiluted with EtOAc
  5. filtrationfiltered through Celite®
  6. washThe filtrate was washed with brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by flash chromatography (SiO2; 0-30% EtOAc in hexanes)

Sources & evidence

ORD record
ord-261e5117cac04f79963c187fdd4de7bf
Source dataset
uspto-grants-2016_08
Patent number
US09428502B2

Reaction notes

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