Dichloromethane → 4-(1-isobutyl-1H-pyrazol-4-yl)aniline

HRID 715752Notes

Reaction equation

HRID 715752 reaction equation
Br[C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][CH:3]=1.[CH2:9]([N:13]1[CH:17]=[C:16](B2OC(C)(C)C(C)(C)O2)[CH:15]=[N:14]1)[CH:10]([CH3:12])[CH3:11].ClCCl.C(=O)([O-])[O-].[Na+].[Na+]>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].O1CCCC1.O.CO>[CH2:9]([N:13]1[CH:17]=[C:16]([C:2]2[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][CH:3]=2)[CH:15]=[N:14]1)[CH:10]([CH3:12])[CH3:11]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 78074-BromoanilineHCID 10340Sodium CarbonateHCID 27593921-Isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Product 1

HCID 633283934-(1-isobutyl-1H-pyrazol-4-yl)aniline

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 21892291Methanol tetrahydrofuran waterSolvent

Conditions

Temperature
85 °C

Procedure

A suspension of 4-bromoaniline (406 mg, 2.362 mmol), 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (650 mg, 2.60 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (57.9 mg, 0.071 mmol) and sodium carbonate (526 mg, 4.96 mmol) in a 6:2:1 mixture of tetrahydrofuran/water/methanol (12 ml) in a microwave vial was subjected to three vacuum/nitrogen purge cycles. The vial was sealed and heated in an oil bath at 85° C. overnight. The mixture was dissolved in a mixture of ethyl acetate (45 ml) and water (20 ml), and the separated aqueous layer was extracted with ethyl acetate (20 ml). The combined organic layers were washed with brine (20 ml), dried with magnesium sulfate, filtered and concentrated. Normal phase chromatography provided the title compound.

Workup

  1. custompurge cycles
  2. customThe vial was sealed
  3. dissolutionThe mixture was dissolved in a mixture of ethyl acetate (45 ml) and water (20 ml)
  4. extractionthe separated aqueous layer was extracted with ethyl acetate (20 ml)
  5. washThe combined organic layers were washed with brine (20 ml)
  6. dry with materialdried with magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-5d78eb3e48f04417a3cc7dc49f97917f
Source dataset
uspto-grants-2015_11
Patent number
US09187472B2

Reaction notes

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