Bromine → 3-(4-Bromo-pyrazol-1-yl)-4-methyl-benzoic acid ethyl ester
Reaction equation
[CH2:1]([O:3][C:4](=[O:17])[C:5]1[CH:10]=[CH:9][C:8]([CH3:11])=[C:7]([N:12]2[CH:16]=[CH:15][CH:14]=[N:13]2)[CH:6]=1)[CH3:2].[Br:18]Br>C(Cl)(Cl)Cl>[CH2:1]([O:3][C:4](=[O:17])[C:5]1[CH:10]=[CH:9][C:8]([CH3:11])=[C:7]([N:12]2[CH:16]=[C:15]([Br:18])[CH:14]=[N:13]2)[CH:6]=1)[CH3:2]Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
A solution of 3-hydrazino-4-methyl benzoic acid (1.0 g, 4.93 mmol), malonaldehyde(bismethylacetate) (0.82 mL, 4.93 mmol), and concentrated HCl (1 mL) in EtOH (20 mL) was heated to reflux for 4 h. After cooling to room temperature, the reaction was poured into ice water, neutralized with 2N NaOH, and extracted with CH2Cl2 (3×). The organic layers were dried over Na2SO4, filtered and concentrated to afford 4-methyl-3-pyrazol-1-yl-benzoic acid ethyl ester (536 mg, 47%) as a yellow oil. A solution of the pyrazole (536 mg, 2.33 mmol) and bromine (0.167 mL, 3.26 mmol) in CHCl3 (15 mL) was refluxed for 4.5 h then cooled to room temperature. The solvent was evaporated to an orange oil. Purification using chromatography on silica gel (1:1 EtOAc/hexanes) yielded 3-(4-bromo-pyrazol-1-yl)-4-methyl-benzoic acid ethyl ester (0.739 g, 99%) as a yellow solid.