Potassium hydride → (E)-3-[4-((S)-1-{2-[3,5-dimethyl-1-(tetrahydropyran-4-ylmethyl)-1H-pyrazol-4-yl]-ethyl}-pyrrolidin-2-yl)-phenyl]-acrylic acid methyl ester

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Reaction Steps

To an ice cold mixture of (E)-3-(4-{(S)-1-[2-(3,5-dimethyl-1H-pyrazol-4-yl)-ethyl]-pyrrolidin-2-yl}-phenyl)-acrylic acid methyl ester (0.85 g, 2.4 mmol) and potassium hydride (115 mg, 2.88 mmol) in 4.0 mL tetrahydrofuran:dimethyl sulfoxide (9:1 v/v) was added 4-bromomethyltetrahydropyran (945 mg, 5.28 mmol). The mixture was slowly warmed to room temperature and stirred under nitrogen for 16 h. It was then quenched with aqueous ammonium chloride and added with ethyl acetate. The layers were separated and the organic layer was washed with more aqueous ammonium chloride. The aqueous layers were then washed with more ethyl acetate and the combined organic extracts were dried over magnesium sulfate and concentrated to a yellow oil. The oil was then purified via silica gel column chromatography (100:0 to 0:100 heptane:ethyl acetate) to give (E)-3-[4-((S)-1-{2-[3,5-dimethyl-1-(tetrahydro-pyran-4-ylmethyl)-1H-pyrazol-4-yl]-ethyl}-pyrrolidin-2-yl)-phenyl]-acrylic acid methyl ester (160 mg, 0.35 mmol, 14% yield) as a yellow oil. LC/MS (m/z): 452.5 (M+1).

Provenance & Evidence