Sodium Carbonate → (3-Fluorophenyl)-[3-(4-methoxyphenyl)-4,5-dihydropyrazol-1-yl]-methanone

HRID 1629974Notes

Reaction equation

HRID 1629974 reaction equation
Cl[C:2]1[CH2:6][CH2:5][N:4]([C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([F:15])[CH:10]=2)=[O:8])[N:3]=1.[CH3:16][O:17][C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][CH:19]=1.C(=O)([O-])[O-].[Na+].[Na+]>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:15][C:11]1[CH:10]=[C:9]([C:7]([N:4]2[CH2:5][CH2:6][C:2]([C:21]3[CH:22]=[CH:23][C:18]([O:17][CH3:16])=[CH:19][CH:20]=3)=[N:3]2)=[O:8])[CH:14]=[CH:13][CH:12]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 201262(4-Methoxyphenyl)boronic acidHCID 711849653-chloro-1-(3-fluorobenzoyl)-4,5-dihydro-1H-pyrazole

Product 1

HCID 71203455(3-Fluorophenyl)-[3-(4-methoxyphenyl)-4,5-dihydropyrazol-1-yl]-methanone

Reagents, catalysts & solvents 1

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalyst

Conditions

Temperature
110 °C

Procedure

To a degassed solution of (3-Chloro-4,5-dihydro-pyrazol-1-yl)-(3-fluoro-phenyl)-methanone (0.19 g, 0.0008 moles, 1 equiv) in dry 1,2-DME-water, 5 mL, (4:1) was added 4-Methoxyphenylboronic acid (0.17 g, 0.0112 moles, 1.4 equiv), anhydrous sodium carbonate (0.17 g, 0.0016 moles, 2 equiv) and Tetrakis-(triphenylphosphine)-palladium (0) (0.092 g, 0.00008 moles, 0.1 equiv). The reaction mixture was heated at 110° C. for 0.5 h under nitrogen atmosphere in microwave conditions or 6-8 h in thermal conditions. Consumption of starting material was confirmed by TLC and LC-MS. 1,2-DME was distilled under reduced pressure, the crude residue was dissolved in dichloromethane (25 mL), washed with water, saturated brine, dried over anhydrous sodium sulfate. The crude product was purified by column chromatography to get the pure compound (3-Fluorophenyl)-[3-(4-methoxyphenyl)-4,5-dihydropyrazol-1-yl]-methanone in 0.100 g. P.S.: (a) In case of Carboxy boronic acid, LiCl (3 eq) was added to the reaction mixture as an additive. (b) In Case of Cyano boronic acid, K3PO4 (2 eq) was used as base.

Workup

  1. customConsumption of starting material
  2. distillation1,2-DME was distilled under reduced pressure
  3. dissolutionthe crude residue was dissolved in dichloromethane (25 mL)
  4. washwashed with water, saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-bc9eea290bbe43938208b037de29677c
Source dataset
uspto-grants-2014_07
Patent number
US08791114B2

Reaction notes

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