Water → methyl 3-(1-methyl-1H-pyrazol-4-yl)-5-(trifluoromethyl)benzoate

HRID 1894959Notes

Reaction equation

HRID 1894959 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].O.[CH3:17][N:18]1[CH:22]=[C:21](B2OC(C)(C)C(C)(C)O2)[CH:20]=[N:19]1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.CCOC(C)=O.CCCCCC>[CH3:17][N:18]1[CH:22]=[C:21]([C:2]2[CH:3]=[C:4]([CH:9]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:11]=2)[C:5]([O:7][CH3:8])=[O:6])[CH:20]=[N:19]1

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 18942156Methyl 3-bromo-5-(trifluoromethyl)benzoate

Product 1

HCID 59439420methyl 3-(1-methyl-1H-pyrazol-4-yl)-5-(trifluoromethyl)benzoateYield 101.9%

Reagents, catalysts & solvents 2

HCID 312751,4-DioxaneSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

To a solution of methyl 3-bromo-5-(trifluoromethyl)benzoate (21.8 g, 77 mmol) in 1,4-dioxane (218 mL), and water (131 mL) were added 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (24 g, 116 mmol), sodium carbonate (27.7 g, 261 mmol) and tetrakis(triphenyphosphine)palladium(0) (4.4 g, 3.8 mmol). The reaction mixture was heated at 80° C. for 3 h after which time TLC (20% EtOAc/hexane) showed consumption of the starting material. The reaction mixture was cooled to room temperature and precipitated solids were removed by filtration. The filtrate was diluted with water and extracted twice with ethyl acetate. The extracts were washed with brine, dried over sodium sulfate, filtered and concentrated. The residue was purified by filtration through silica, eluting with 0% to 40% ethyl acetate in hexanes to provide methyl 3-(1-methyl-1H-pyrazol-4-yl)-5-(trifluoromethyl)benzoate as a pale yellow solid (22.3 g, 100%). LC-MS (FA): ES+ 285; 1H NMR (400 MHz, CDCl3) δ ppm 8.29 (s, 1H), 8.14 (s, 1H), 7.87 (s, 1H), 7.86 (s, 1H), 7.76 (s, 1H), 4.01 (s, 3H), 3.98 (s, 3H).

Workup

  1. customconsumption of the starting material
  2. customprecipitated solids
  3. customwere removed by filtration
  4. additionThe filtrate was diluted with water
  5. extractionextracted twice with ethyl acetate
  6. washThe extracts were washed with brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. filtrationThe residue was purified by filtration through silica
  11. washeluting with 0% to 40% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-2205fa8303a14523b4301cb45966cbc5
Source dataset
uspto-grants-2013_08
Patent number
US08513421B2

Reaction notes

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