Hydrochloric Acid → 2-(2,6-Dichloro-phenyl)-4-isopropyl-2H-pyrazole-3-carboxylic acid methyl ester

HRID 1689757Notes

Reaction equation

HRID 1689757 reaction equation
[CH2:1]([O:3][C:4](=[O:15])[C:5](=O)[C:6]([CH:11]([CH3:13])[CH3:12])=[CH:7][N:8](C)C)C.Cl.[Cl:17][C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([Cl:24])[C:19]=1[NH:25]N.Cl>CCO>[CH3:1][O:3][C:4]([C:5]1[N:25]([C:19]2[C:18]([Cl:17])=[CH:23][CH:22]=[CH:21][C:20]=2[Cl:24])[N:8]=[CH:7][C:6]=1[CH:11]([CH3:13])[CH3:12])=[O:15]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 2723909(2,6-Dichlorophenyl)hydrazine monohydrochlorideHCID 765400773-Isopropyl-4-dimethylamino-2-oxo-but-3-enoic acid ethyl ester

Product 1

HCID 574432552-(2,6-Dichloro-phenyl)-4-isopropyl-2H-pyrazole-3-carboxylic acid methyl esterYield 52%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 4-methyl-2-oxo-pentanoic acid methyl ester (3.8 g, 26 mmol) in N,N-dimethylformamide dimethyl acetal (7 mL, 52 mmol) is added p-toluenesulfonic acid monohydrate (30 mg). The mixture is stirred at 80° C. overnight. The reaction mixture is concentrated under reduced pressure to give 3-isopropyl-4-dimethylamino-2-oxo-but-3-enoic acid ethyl ester as an orange oil. To a solution of 3-isopropyl-4-dimethylamino-2-oxo-but-3-enoic acid ethyl ester and 2,6-dichlorophenylhydrazine hydrochloride (2.8 g, 13 mmol) in EtOH (40 mL) is added concentrated HCl (0.5 mL). The mixture is stirred at ambient temperature for 2 h followed by refluxing overnight. The reaction mixture is concentrated and the residue is partitioned between EtOAc and 1N HCl. The organic phase is dried (Na2SO4) and concentrated to a residue. The residue is purified by column chromatography (0-15% EtOAc in hexanes) to give the title compound as an oil (2.2 g, 52%). 1H NMR (CDCl3): δ 7.76 (s, 1H), 7.43 (d, 2H), 7.34 (dd, 1H), 3.75 (s, 3H), 3.48 (m, 1H), 1.32 (d, 6H).

Workup

  1. temperatureby refluxing overnight
  2. concentrationThe reaction mixture is concentrated
  3. customthe residue is partitioned between EtOAc and 1N HCl
  4. dry with materialThe organic phase is dried (Na2SO4)
  5. concentrationconcentrated to a residue
  6. customThe residue is purified by column chromatography (0-15% EtOAc in hexanes)

Sources & evidence

ORD record
ord-6f9dbe5c17214a77ab9befb6440782f5
Source dataset
uspto-grants-2012_04
Patent number
US08153624B2

Reaction notes

Loading…