Potassium Phosphate, Tribasic → 3-(1-(3-methoxyphenyl)-1H-pyrazol-4-yl)pyridine

HRID 1050641Notes

Reaction equation

HRID 1050641 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=2)O1.Br[C:17]1[CH:18]=[N:19][N:20]([C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([O:28][CH3:29])[CH:23]=2)[CH:21]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>[CH3:29][O:28][C:24]1[CH:23]=[C:22]([N:20]2[CH:21]=[C:17]([C:9]3[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=3)[CH:18]=[N:19]2)[CH:27]=[CH:26][CH:25]=1

Participants

8

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27346563-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 665213344-Bromo-1-(3-methoxyphenyl)pyrazole

Product 1

HCID 1180074013-(1-(3-methoxyphenyl)-1H-pyrazol-4-yl)pyridineYield 96.3%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 131736070tricyclohexylphosphine PCy3CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a three-necked flask equipped with a magnetic stir bar and a condenser was added 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (1230 mg, 6.0 mmol, 1.2 eq), Pd2(dba)3 (183 mg, 0.2 mmol, 0.04 eq) and tricyclohexylphosphine PCy3 (135 mg, 0.48 mmol, 0.096 eq). Then the flask was evacuated and backfilled with nitrogen. The evacuation and back fill procedure was repeated another two times. Then a solution of 4-bromo-1-(3-methoxyphenyl)-1H-pyrazole 3 (1266 mg, 5.0 mmol, 1.0 eq) in dioxane (25 mL) and a solution of K3PO4 (1804 mg, 8.5 mmol, 1.7 eq) in H2O (10 mL) were added by syringe independently under nitrogen. The mixture was stirred in an oil bath at a temperature of 95-105° C. for 24 hours, cooled down to ambient temperature, filtered and washed with ethyl acetate. The organic layer of the filtrate was separated, dried over sodium silphate, filtered, concentrated and the residue was purified through column chromatography on silica gel using hexane/ethyl acetate (10:1-5:1) first, then dichloromethane/methanol (10:1) as eluent to obtain the desired product 3-(1-(3-methoxyphenyl)-1H-pyrazol-4-yl)pyridine 4 as a brown solid 1.21 g in 96% yield. 1H NMR (DMSO-d6, 400 MHz): δ 3.85 (s, 3H), 6.90-6.93 (m, 1H), 7.41-7.48 (m, 4H), 8.10 (dt, J=8.0, 2.0 Hz, 1H), 8.31 (s, 1H), 8.45 (dd, J=4.8, 1.6 Hz, 1H), 8.98 (d, J=1.2 Hz, 1H), 9.13 (s, 1H).

Workup

  1. customTo a three-necked flask equipped with a magnetic stir bar and a condenser
  2. customThen the flask was evacuated
  3. temperaturecooled down to ambient temperature
  4. filtrationfiltered
  5. washwashed with ethyl acetate
  6. customThe organic layer of the filtrate was separated
  7. dry with materialdried over sodium silphate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customthe residue was purified through column chromatography on silica gel

Sources & evidence

ORD record
ord-07656818a33142fa966e1016caf4db1b
Source dataset
uspto-grants-2016_07
Patent number
US09385329B2

Reaction notes

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