Sodium Chloride → 3-Chloro-1-(pyridine-3-yl)-4,5-dihydro-1H-pyrazole-5-carbonitrile

HRID 1773177Notes

Reaction equation

HRID 1773177 reaction equation
[ClH:1].[N:2]1[CH:7]=[CH:6][CH:5]=[C:4]([NH:8]/[N:9]=[CH:10]/[C:11](O)=O)[CH:3]=1.Cl[N:15]1C(=O)C[CH2:17][C:16]1=O.C(#N)C=C.C(=O)(O)[O-].[K+].[Cl-].[Na+]>C(OCC)(=O)C.O>[Cl:1][C:10]1[CH2:11][CH:17]([C:16]#[N:15])[N:8]([C:4]2[CH:3]=[N:2][CH:7]=[CH:6][CH:5]=2)[N:9]=1

Participants

8

Reactant 5

HCID 5234Sodium ChlorideHCID 7855AcrylonitrileHCID 31398ChlorosuccinimideHCID 516893Potassium BicarbonateHCID 118022438(2E)-2-(pyridin-3-ylhydrazinylidene)acetic acid;hydrochloride

Product 1

HCID 1180227713-Chloro-1-(pyridine-3-yl)-4,5-dihydro-1H-pyrazole-5-carbonitrileYield 71.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

(E)-2-((2-Pyridin-3-yl)hydrazono)acetic acid hydrochloride (2.00 g, 9.42 mmol) was stirred in ethyl acetate (47.1 mL). N-Chlorosuccinimide (2.36 g, 19.3 mmol), acrylonitrile (1.85 mL, 28.3 mmol) and potassium bicarbonate (2.86 g, 28.3 mmol) were added. Water (0.05 mL) was added and the mixture was stirred at room temperature for 18 hours. Saturated aqueous sodium chloride (brine, 50 mL) was added and the mixture was filtered through Celite®. The filter cake was washed with ethyl acetate (40 mL) and the layers were separated. The organic layers were combined, dried and concentrated to afford a residue. The resulting residue was purified by flash column chromatography using 80-100% ethyl acetate/hexanes as eluent to afford the desired product as an orange solid (1.40 g, 57.5%): 1H NMR (400 MHz, CDCl3) δ 8.51 (dd, J=2.9, 0.7 Hz, 1H), 8.33 (dd, J=4.7, 1.4 Hz, 1H), 7.51 (ddd, J=8.4, 2.9, 1.4 Hz, 1H), 7.30 (ddd, J=8.5, 4.7, 0.8 Hz, 1H), 5.06 (dd, J=11.3, 5.9 Hz, 1H), 3.64 (dd, J=17.4, 11.3 Hz, 1H), 3.51 (dd, J=17.4, 5.9 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 143.34, 142.79, 140.11, 136.16, 123.92, 121.93, 115.80, 51.39, 43.04; ESIMS m/z 207 ([M+H]+).

Workup

  1. filtrationthe mixture was filtered through Celite®
  2. washThe filter cake was washed with ethyl acetate (40 mL)
  3. customthe layers were separated
  4. customdried
  5. concentrationconcentrated
  6. customto afford a residue
  7. customThe resulting residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-9510907865df4449a8320894d1eb68bb
Source dataset
uspto-grants-2016_02
Patent number
US09255083B2

Reaction notes

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