Cesium carbonate → 1-(4-methoxy-2-methylphenyl)-4-(trifluoromethyl)-1H-pyrazole

HRID 537452Notes

Reaction equation

HRID 537452 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[CH3:10].[F:11][C:12]([F:19])([F:18])[C:13]1[CH:14]=[N:15][NH:16][CH:17]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O.O.[Cu]=O>[CH3:9][O:8][C:5]1[CH:6]=[CH:7][C:2]([N:15]2[CH:14]=[C:13]([C:12]([F:19])([F:18])[F:11])[CH:17]=[N:16]2)=[C:3]([CH3:10])[CH:4]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 1179151-Bromo-4-methoxy-2-methylbenzeneHCID 127777954-(Trifluoromethyl)-1H-pyrazole

Product 1

HCID 681566421-(4-methoxy-2-methylphenyl)-4-(trifluoromethyl)-1H-pyrazoleYield 29%

Reagents, catalysts & solvents 3

HCID 14829Copper oxideCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

To a mixture of 1-bromo-4-methoxy-2-methylbenzene (1.5 g, 7.5 mmol) in N,N-dimethylformamide (15 mL) was added 4-(trifluoromethyl)-1H-pyrazole (1.12 g, 8.21 mmol), copper(II) oxide (107 mg, 0.746 mmol), and cesium carbonate (4.86 g, 14.9 mmol). The mixture was heated in a microwave to 120° C. for 1 hour. The mixture was diluted with water (20 mL) and extracted with ethyl acetate (3×30 mL). The combined organics were dried over sodium sulfate, filtered, and concentrated. Purification by column chromatography gave 1-(4-methoxy-2-methylphenyl)-4-(trifluoromethyl)-1H-pyrazole (550 mg, 29%) as a white solid. 1H NMR (400 MHz, CDCl3, δ): 7.81 (s, 1H), 7.74 (s, 1H), 7.16 (m, 1H), 6.74 (m, 2H), 3.77 (s, 3H), 2.10 (s, 3H).

Workup

  1. extractionextracted with ethyl acetate (3×30 mL)
  2. dry with materialThe combined organics were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification by column chromatography

Sources & evidence

ORD record
ord-419dde8f1ebc467a8930bd59d5674778
Source dataset
uspto-grants-2014_10
Patent number
US08859591B2

Reaction notes

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