Cesium carbonate → 1-methyl-4-(3-nitro-5-(trifluoromethyl)phenyl)-1H-pyrazole

HRID 1050192Notes

Reaction equation

HRID 1050192 reaction equation
Br[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[C:4]([N+:12]([O-:14])=[O:13])[CH:3]=1.[CH3:15][N:16]1[CH:20]=[C:19](B2OC(C)(C)C(C)(C)O2)[CH:18]=[N:17]1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.O.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]>[CH3:15][N:16]1[CH:20]=[C:19]([C:2]2[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[C:4]([N+:12]([O-:14])=[O:13])[CH:3]=2)[CH:18]=[N:17]1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 70154111-Bromo-3-nitro-5-(trifluoromethyl)benzene

Product 1

HCID 904231661-methyl-4-(3-nitro-5-(trifluoromethyl)phenyl)-1H-pyrazoleYield 29.9%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
100 °C

Procedure

A suspension of 1-bromo-3-nitro-5-(trifluoromethyl)benzene (1 g, 3.70 mmol) in 1,4-dioxane (12 mL) and water (4 mL) was added to a solution of 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.771 g, 3.70 mmol) in 1,4-dioxane (12 mL) and water (4 mL). PdCl2(dppf) (0.271 g, 0.370 mmol) and Cs2CO3 (2.413 g, 7.41 mmol) were added and the mixture was heated at 100° C. for 20 min. The mixture was then cooled to rt. Then the solution was concentrated and distributed between EA and saturated NaHCO3 solution. The combined organic extracts were washed with brine, dried over MgSO4, filtered and concentrated. The crude material was purified by silica column chromatography (PE/EA=1:1). All fractions found to contain product by TLC (PE/EA=5:1, Rf=0.3) were combined and concentrated to yield a light yellow solid of 1-methyl-4-(3-nitro-5-(trifluoromethyl)phenyl)-1H-pyrazole (300 mg, 1.106 mmol, 29.9% yield): 1H NMR (400 MHz, CDCl3) δ 8.47 (s, 1H), 8.31 (s, 1H), 7.99 (s, 1H), 7.89 (s, 1H), 7.81 (s, 1H), 4.01 (s, 3H). ES-LCMS m/z 272 (M+H).

Workup

  1. temperatureThe mixture was then cooled to rt
  2. concentrationThen the solution was concentrated
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was purified by silica column chromatography (PE/EA=1:1)
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-3a47a3cf84674b09ac93fdeed6e4c4b9
Source dataset
uspto-grants-2016_07
Patent number
US09382238B2

Reaction notes

Loading…