Dimethylformamide → 3-(3-chloro-1H-pyrazol-1-yl)pyridine

HRID 1482403Notes

Reaction equation

HRID 1482403 reaction equation
[Cl:1][C:2]1[CH2:6][CH2:5][N:4]([C:7]2[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=2)[N:3]=1.CN(C)C=O.S(OOS([O-])(=O)=O)([O-])(=O)=O.[K+].[K+]>O.[OH-].[Na+]>[Cl:1][C:2]1[CH:6]=[CH:5][N:4]([C:7]2[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=2)[N:3]=1

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 24412Potassium PersulfateHCID 118022928HCID 118022928, compound

Product 1

HCID 674995403-(3-chloro-1H-pyrazol-1-yl)pyridineYield 54%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 14798Sodium HydroxideSolvent2×

Conditions

Temperature
80 °C

Procedure

A 100 mL, 3-neck round bottom flask was charged with 3-(3-chloro-4,5-dihydro-1H-pyrazol-1-yl)pyridine (3.0 g) and N,N-dimethylformamide (15 mL). potassium persulfate (6.70 g, 24.8 mmol) was added and the reaction was heated to 80° C. for 3 hours. An exotherm at about 110° C. was observed. It was allowed to cool to 80° C. and stirred at 80° C. for 3 hours, at which point a sample was diluted with water and basified with 50 wt % sodium hydroxide solution and extracted with ethyl acetate. The organic layer was analyzed by thin layer chromatography [Eluent: ethyl acetate], which showed that the desired product was formed as the major product, along with a trace of starting material and some minor impurities. The reaction mixture was cooled to 20° C. and diluted with water (50 mL). It was basified with 50% sodium hydroxide and extracted with ethyl acetate (4×30 mL). The organic layers were combined, concentrated to dryness, and purified by flash column chromatography using 30% ethyl acetate/hexanes as eluent. The pure fractions were concentrated to dryness to afford a white solid (1.60 g, 54%): mp 104-106° C.; 1H NMR (400 MHz, CDCl3) δ 8.93 (d, J=27 Hz, 1H), 8.57 (dd, J=4.8, 1.4 Hz, 1H), 8.02 (ddd, J=8.3, 2.7, 1.5 Hz, 1H), 7.91 (d, J=2.6 Hz, 1H), 7.47-7.34 (M, 1H), 6.45 (d, J=2.6 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 148.01, 142.72, 140.12, 135.99, 128.64, 126.41, 124.01, 108.08; EIMS m/z 179 ([M]+).

Workup

  1. customat about 110° C.
  2. temperatureto cool to 80° C.
  3. extractionextracted with ethyl acetate
  4. customwas formed as the major product, along with a trace of starting material
  5. temperatureThe reaction mixture was cooled to 20° C.
  6. extractionextracted with ethyl acetate (4×30 mL)
  7. concentrationconcentrated to dryness
  8. custompurified by flash column chromatography
  9. concentrationThe pure fractions were concentrated to dryness

Sources & evidence

ORD record
ord-7128c26b9e4c4e53a0ec18395f28eef9
Source dataset
uspto-grants-2016_08
Patent number
US09414594B2

Reaction notes

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