反应详情

To a stirred solution of 1-(4-iodobenzyl)-3,5-dimethyl-1H-pyrazol-4-yl-acetic acid tert.-butyl ester (12.2 g) in tetrahydrofuran (100 ml) at room temperature is added diisopropylethylamine (12.3 ml). The solution is degassed and put under argon. Ethynyltrimethylsilane (4.5 ml), copper(I)iodide (543 mg) and bis-(triphenylphosphine)-palladiumdichloride (1.0 g) are added. After 15 h of stirring, the reaction is absorbed onto Extrelute and purified by flash chromatography (4:1 isocratic-cyclohexane:ethyl acetate) to yield a solid (10.7 g; [M+H]=397; HPLC retention time 1.71 min (Method J)). The solid is dissolved in tetrahydrofuran (200 ml) and is stirred together with tetrabutylammonium fluoride (1 M in THF, 28 ml). After 15 h at room temperature, the reaction mixture is concentrated in vacuo. The residue is purified by flash chromatography (4:1 isocratic-cyclohexane:ethyl acetate) to yield 1-(4-ethynylbenzyl)-3,5-dimethyl-1H-pyrazol-4-yl-acetic acid tert.-butyl ester (6.8 g; [M+H]=325; HPLC retention time 1.47 min (Method J)).

1. customThe solution is degassed
2. additionEthynyltrimethylsilane (4.5 ml), copper(I)iodide (543 mg) and bis-(triphenylphosphine)-palladiumdichloride (1.0 g) are added
3. customthe reaction is absorbed onto Extrelute
4. custompurified by flash chromatography (4:1 isocratic-cyclohexane:ethyl acetate)
5. customto yield a solid (10.7 g; [M+H]=397; HPLC retention time 1.71 min (Method J))
6. waitAfter 15 h at room temperature
7. concentrationthe reaction mixture is concentrated in vacuo
8. customThe residue is purified by flash chromatography (4:1 isocratic-cyclohexane:ethyl acetate)