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

HRID 1473281Notes

Reaction equation

HRID 1473281 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+]>>[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

4

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%

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; Combi-blocks, San Diego, Calif.), 1-methyl-1H-pyrazole-5-boronic acid pinacol ester (3.41 g, 16.39 mmol), potassium phosphate (6.05 g, 28.5 mmol) and Pd(dppf)Cl2CH2Cl2 (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, and then stirred at room temperature for 48 h. The mixture was diluted with water and extracted with EtOAc (three times). The combined organics were washed with brine, dried and concentrated under a vacuum. The product was purified by chromatography using 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) as a brown solid. 1H NMR (400 MHz, DMSO-d6) δ ppm=8.06 (td, J=0.7, 8.1 Hz, 1H), 7.86-7.73 (m, 2H), 7.53 (d, J=2.0 Hz, 1H), 6.41 (d, J=2.0 Hz, 1H), 3.64 (s, 3H); 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 (three times)
  6. washThe combined organics were washed with brine
  7. customdried
  8. concentrationconcentrated under a vacuum
  9. customThe product was purified by chromatography

Sources & evidence

ORD record
ord-b694013f2c784db6a68f2704b7e705f2
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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