Acetonitrile → ethyl 3-bromo-1-(3,5-dichloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate

HRID 453081Notes

Reaction equation

HRID 453081 reaction equation
C(#N)C.[Cl:4][C:5]1[C:6]([N:12]2[CH:16]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:15][C:14](=O)[NH:13]2)=[N:7][CH:8]=[C:9]([Cl:11])[CH:10]=1.P(Br)(Br)([Br:25])=O.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl.O>[Br:25][C:14]1[CH2:15][CH:16]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[N:12]([C:6]2[C:5]([Cl:4])=[CH:10][C:9]([Cl:11])=[CH:8][N:7]=2)[N:13]=1

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 10340Sodium CarbonateHCID 24613Phosphorus oxybromideHCID 58158924Ethyl 2-(3,5-dichloropyridin-2-yl)-5-oxopyrazolidine-3-carboxylate

Product 1

HCID 58158936ethyl 3-bromo-1-(3,5-dichloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylateYield 67%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a 250 mL flask, acetonitrile (65 mL), ethyl 2-(3,5-dichloropyridin-2-yl)-5-oxopyrazolidine-3-carboxylate (3.0 g, 9.8 mmol, the product of Step (3), Example 3) and phosphoryl bromide (2.8 g, 9.8 mmol) were added. The reaction mixture was heated to reflux for 2 hours. The reaction mixture was distilled to remove 30 mL solvent and added to the mixture of sodium carbonate (10 g, 120 mmol) and water (40 mL). The mixture was stirred for 20 minutes until no gas released. The reaction mixture was diluted with dichloromethane (100 mL), stirred for 50 minutes and extracted with dichloromethane (3×100 mL). The organic layer was washed with water, dried over anhydrous magnesium sulfate, and concentrated under vacuum to give the product (2.4 g) as amber oil in 67% yield. 1H NMR (300 MHz, CDCl3): 8.027 (d, 1H), 7.673 (d, 1H), 5.201 (dd, 1H), 4.202 (q, 2H), 3.464 (dd, 1H), 3.248 (dd, 1H), 1.223 (t, 3H).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 2 hours
  3. distillationThe reaction mixture was distilled
  4. customto remove 30 mL solvent
  5. stirringstirred for 50 minutes
  6. extractionextracted with dichloromethane (3×100 mL)
  7. washThe organic layer was washed with water
  8. dry with materialdried over anhydrous magnesium sulfate
  9. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-3f3f0ded7ea042c88beedaa06fd19b5c
Source dataset
uspto-grants-2013_07
Patent number
US08492409B2

Reaction notes

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