Sodium Fluoride → (2S,4S)-1-Benzyl 2-methyl 4-fluoropyrrolidine-1,2-dicarboxylate

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Reaction Steps

Methyl(2S,4R)-1-benzyloxycarbonyl-4-hydroxypyrrolidine-2-carboxylate (306 mg, 0.00108 mol) and sodium fluoride (55 mg, 0.00131 mol) were suspended in dichloromethane (1.8 mL), followed by addition of Ishikawa reagent (293 mg, 0.00131 mol) under ice cooling. The reaction mixture was slowly warmed to room temperature and then stirred for 20 hours. After the reaction, the reaction mixture was poured into ice-cold saturated aqueous sodium bicarbonate (5 mL) and then separated into organic and aqueous layers. The aqueous layer was extracted with ethyl acetate. This extracted solution was combined with the organic layer obtained above, washed sequentially with 10% aqueous potassium bisulfate and saturated aqueous sodium chloride, and then dried over anhydrous sodium sulfate. After drying, the solvent and the decomposition product of Ishikawa reagent (N,N-diethyl-2,3,3,3-tetrafluoropropionamide) were distilled off under reduced pressure, and the residue was applied to silica gel column chromatography (developing solvent; hexane:ethyl acetate=5:1 to 0:1) to give the titled compound (227 mg, colorless oil).

Provenance & Evidence