Cesium carbonate → 1-(6-(trifluoromethyl)pyridin-3-yl)-1H-pyrazole-3-carbaldehyde

HRID 57415Notes

Reaction equation

HRID 57415 reaction equation
[NH:1]1[CH:5]=[CH:4][C:3]([CH:6]=[O:7])=[N:2]1.Br[C:9]1[CH:10]=[CH:11][C:12]([C:15]([F:18])([F:17])[F:16])=[N:13][CH:14]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CN[C@@H]1CCCC[C@H]1NC.[Cl-].[NH4+]>CN(C=O)C.[Cu]I>[F:16][C:15]([F:18])([F:17])[C:12]1[N:13]=[CH:14][C:9]([N:1]2[CH:5]=[CH:4][C:3]([CH:6]=[O:7])=[N:2]2)=[CH:10][CH:11]=1

Participants

8

Reactant 5

HCID 10796Cesium carbonateHCID 25517Ammonium ChlorideHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 27611975-Bromo-2-(trifluoromethyl)pyridineHCID 122183831H-Pyrazole-3-carbaldehyde

Product 1

HCID 904146611-(6-(trifluoromethyl)pyridin-3-yl)-1H-pyrazole-3-carbaldehydeYield 27%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 1H-pyrazole-3-carbaldehyde (0.700 g, 7.29 mmol), 5-bromo-2-(trifluoromethyl)pyridine (2.31 g, 10.2 mmol, 1.4 equiv), cesium carbonate (4.75 g, 14.6 mmol, 2.0 equiv), copper(I) iodide (0.069 g, 0.36 mmol, 0.05 equiv), and (1R,2R)—N1,N2-dimethylcyclohexane-1,2-diamine (0.23 mL, 1.46 mmol, 0.2 equiv) in DMF (9.5 mL) was heated in a sealed reaction vessel at 110° C. for 16 hours. The reaction was then cooled to room temperature and saturated aqueous ammonium chloride (100 mL) was added. The mixture was extracted with ethyl acetate (3×50 mL). The combined organic extracts were washed with saturated aqueous sodium chloride (50 mL), dried (Na2SO4), filtered, and concentrated in vacuo. Silica gel column chromatography (EtOAc/heptane) provided 1-(6-(trifluoromethyl)pyridin-3-yl)-1H-pyrazole-3-carbaldehyde (0.470 g, brown solid) in 27% yield. 1H NMR (400 MHz, CDCl3) δ 10.13 (s, 1H), 9.18 (d, J=2.1 Hz, 1H), 8.34 (dd, J=8.7, 2.0 Hz, 1H), 8.12 (m, 1H), 7.88 (d, J=8.5 Hz, 1H), 7.10 (d, J=1.8 Hz, 1H). MS m/z 241.9 (M+H)+; Rt-0.78 min.

Workup

  1. temperatureThe reaction was then cooled to room temperature
  2. extractionThe mixture was extracted with ethyl acetate (3×50 mL)
  3. washThe combined organic extracts were washed with saturated aqueous sodium chloride (50 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d185527d654b4503b978edd4feb22477
Source dataset
uspto-grants-2016_09
Patent number
US09434719B2

Reaction notes

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