1H-pyrazole-1-acetic acid, 4-iodo- synthesis

Yield:6752-13-2 82%

Reaction Conditions:

Stage #1: 4-iodopyrazole;bromoacetic acid tert-butyl esterwith caesium carbonate in acetonitrile at 80; for 12 h;
Stage #2: with trifluoroacetic acid in acetonitrile at 20; for 1 h;

Steps:

13

To a round-bottomed flask, compound 4-iodopyrazoie (970 mg, 5.() mmoi, 1.0 eq) and tert-butyl bromoacetate (878 mg, 4.5 mmoi, 0.9 eq) were mixed in 20 rnL of acetomtrie, then cesium carbonate (1.95 g. 6.0 mmoi, 1.2 eq) was added. The solution was stirred at 80 °C for 12 h. The solvent was removed by rotary evaporator. The residue was partitioned between DCM and saturated brine. The combined organic layer was dried. The filtered solution was concentrated and purified by flash column chromatography with hexane/ ethyl acetate to get compound 2-(4-iodo-IH-pyrazol-1- yl)acetic acid (1.25 g, 82% yield). The above obtained compound was dissolved in 10 mL of TFA. The solution was stirred at room temperature for I h. The solvent was removed by rotary evaporator to afford the residue, which was used in next step without further purification. UPLC-MS calculated for C5Fi6iNO2 [M+1I : 252,95, found 253.01.

References:

WO2019/55444,2019,A1 Location in patent:Paragraph 0401-402