Potassium Phosphate, Tribasic → 5-(2-bromo-5-(trifluoromethyl)phenyl)-1-methyl-1H-pyrazole

HRID 1524390Notes

Reaction equation

HRID 1524390 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1I.[CH3:13][N:14]1[C:18](B2OC(C)(C)C(C)(C)O2)=[CH:17][CH:16]=[N:15]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>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].C(Cl)Cl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[C:18]1[N:14]([CH3:13])[N:15]=[CH:16][CH:17]=1

Participants

5

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 49129081-methyl-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 467352311-Bromo-2-iodo-4-(trifluoromethyl)benzene

Product 1

HCID 712595845-(2-bromo-5-(trifluoromethyl)phenyl)-1-methyl-1H-pyrazoleYield 68%

Reagents, catalysts & solvents 1

HCID 178418807HCID 178418807, compoundCatalyst

Conditions

Temperature
60 °C

Procedure

A round-bottom flask was charged with 1-bromo-2-iodo-4-(trifluoromethyl)benzene (5.00 g, 14.25 mmol), 1-methyl-1h-pyrazole-5-boronic acid pinacol ester (3.41 g, 16.39 mmol), potassium phosphate (6.05 g, 28.5 mmol) and PdCl2(dppf)-CH2Cl2 (1.164 g, 1.425 mmol). The flask was flushed with Ar, and DMF (47.5 ml) was then added. The flask was sealed, heated to 60° C. for 12 h, then stirred at room temperature for 48 h. The mixture was diluted with water and extracted with EtOAc (3×). The combined organics were washed with brine, dried, and concentrated in vacuo. The crude product was purified by chromatography on silica gel (0 to 100% EtOAc/Heptane) to yield 5-(2-bromo-5-(trifluoromethyl)phenyl)-1-methyl-1H-pyrazole (2.956 g, 9.69 mmol, 68.0% yield) as a brown solid. 1H NMR (400 MHz, DMSO-d6) δ=8.06 (td, J=0.7, 8.1 Hz, 1 H), 7.86-7.73 (m, 2 H), 7.53 (d, J=2.0 Hz, 1 H), 6.41 (d, J=2.0 Hz, 1 H), 3.64 (s, 3 H). m/z (ESI) 305.0 (M+H)+.

Workup

  1. customThe flask was flushed with Ar, and DMF (47.5 ml)
  2. additionwas then added
  3. customThe flask was sealed
  4. additionThe mixture was diluted with water
  5. extractionextracted with EtOAc (3×)
  6. washThe combined organics were washed with brine
  7. customdried
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by chromatography on silica gel (0 to 100% EtOAc/Heptane)

Sources & evidence

ORD record
ord-4198a8261f3b42e59238a89e411c3d00
Source dataset
uspto-grants-2015_07
Patent number
US09079902B2

Reaction notes

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