Sodium hydride → HCID 69593388, compound

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Reaction Steps

Sodium hydride (12 mg of 60% dispersion in oil, 0.3 mmol) was added to a stirred solution of 3-phenylpyrrole (43 mg, 0.30 mmol) in tetrahydrofuran (1.0 ml) under nitrogen. The mixture was stirred for 15 minutes then added via cannula to a stirred solution of the (3R)-3-isobutyldihydrofuran-2,5-dione (0.2 mmol) in tetrahydrofuran (1.0 ml) at 0° C., then stirred for 5 hours. The majority of solvents were removed in vacuo then water (10 ml) added. The aqueous layer was extracted with ethyl acetate (5 ml) then saturated aqueous sodium chloride solution (5 ml) added and the aqueous layer extracted with an additional portion of ethyl acetate (5 ml). The aqueous layer was acidified using hydrochloric acid (1M) to pH=1 then the product extracted into ethyl acetate (2×5 ml), dried (MgSO4) and the solvent removed in vacuo. The residue was purified by flash chromatography over silica gel eluting with a gradient of methanol:dichloromethane 1:99→3:17. Appropriate fractions were combined and the solvents removed in vacuo to leave a mixture (approximately 1:1) of (2R)-4-methyl-2-[oxo-2-(3-phenylpyrrol-1-yl)ethyl]pentanoic acid and (3S)-5-Methyl-3-(3-phenyl-pyrrole-1-carbonyl)-hexanoic acid (1.6 mg, 2%) as an oil. TLC (two spots, Rf=0.8 and Rf=0.75, methanol:dichloromethane 1:9), analytical HPLC two unresolved UV peaks with Rt=19.020 and 19.127 mins, HPLC-MS (two unresolved UV peaks with Rt=9.724 and 9.861 mins, 300.2 [M+H]+, 621.3 [2M+Na]+).

Provenance & Evidence