[3-(Trifluoromethoxy)phenyl]hydrazine → 5-cyclopropyl-3-methyl-1-(3-trifluoromethoxy-phenyl)-1H-pyrazole-4-carboxylic acid ethyl ester

HRID 1011878Notes

Reaction equation

HRID 1011878 reaction equation
[CH2:1]([O:3][C:4](=[O:14])[CH:5]([C:9]([CH:11]1[CH2:13][CH2:12]1)=O)[C:6](=O)[CH3:7])[CH3:2].[F:15][C:16]([F:27])([F:26])[O:17][C:18]1[CH:19]=[C:20]([NH:24][NH2:25])[CH:21]=[CH:22][CH:23]=1>C(O)(=O)C>[CH2:1]([O:3][C:4]([C:5]1[C:6]([CH3:7])=[N:25][N:24]([C:20]2[CH:21]=[CH:22][CH:23]=[C:18]([O:17][C:16]([F:15])([F:27])[F:26])[CH:19]=2)[C:9]=1[CH:11]1[CH2:13][CH2:12]1)=[O:14])[CH3:2]

Participants

4

Reactant 2

HCID 5194226[3-(Trifluoromethoxy)phenyl]hydrazineHCID 669015882-Cyclopropanecarbonyl-3-oxo-butyric acid ethyl ester

Product 1

HCID 673145905-cyclopropyl-3-methyl-1-(3-trifluoromethoxy-phenyl)-1H-pyrazole-4-carboxylic acid ethyl esterYield 79%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent2×

Procedure

To a solution of intermediate 11A, 2-cyclopropanecarbonyl-3-oxo-butyric acid ethyl ester (2.0 g, 10 mmol) in acetic acid (10 ml), cooled at 5° C., was added a solution of (3-Trifluoromethoxy-phenyl)-hydrazine (2.1 g, 11 mmol) in acetic acid (10 ml). The reaction was allowed to come to room temperature (1 h) after which time the reaction was concentrated, the residue dissolved in DCM, washed with saturated NaHCO3, (Na2SO4) and concentrated. Purification by flash column chromatography (EtOAc:n-heptane 1:9) afforded 5-cyclopropyl-3-methyl-1-(3-trifluoromethoxy-phenyl)-1H-pyrazole-4-carboxylic acid ethyl ester (2.8 g, 77%). Saponification of the ester with NaOH in analogy to intermediate 6 affords the title compound.

Workup

  1. customto come to room temperature
  2. custom(1 h)
  3. concentrationwas concentrated
  4. dissolutionthe residue dissolved in DCM
  5. washwashed with saturated NaHCO3, (Na2SO4)
  6. concentrationconcentrated
  7. customPurification by flash column chromatography (EtOAc:n-heptane 1:9)

Sources & evidence

ORD record
ord-dc2d47f25dc8459bbfabb9570262c1fc
Source dataset
uspto-grants-2011_07
Patent number
US07977358B2

Reaction notes

Loading…