Hydrochloric Acid → 2-(4-Fluoro-benzenesulfonyl)-2-aza-spiro[3.3]heptane

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Reaction Conditions

Reaction Steps

To a cooled (ice-water bath) solution of 4-fluoro-benzenesulfonamide (320 mg, 1.83 mmol) in N,N-dimethylformamide (5 mL), was added sodium hydride (150 mg, 60% dispersion, 3.75 mmol) portion-wise. After the mixture was stirred at 0° C. for 10 minutes, a solution of 3,3-bis-bromomethyl-oxetane (440 mg, 1.8 mmol) in N,N-dimethylformamide (3 mL) was added. The resulting mixture was stirred at room temperature overnight, then neutralized with 1 N hydrochloric acid, and extracted with ethyl acetate (20 mL×3). The combined organic layers were washed with brine (20 mL×3), dried over sodium sulfate, and concentrated in vacuo. The residue was purified by flash column chromatography (elution with 20% ethyl acetate in petroleum ether) to afford 2-(4-fluoro-benzenesulfonyl)-2-aza-spiro[3.3]heptane (120 mg, 26%) as a white solid (reference: Blizzard T. A. et al., Bioorg. Med. Chem. Lett. 14 (2004) 3861-3864), MS cald, for C12H14FNO2S 255, obsd. (ESI+) [(M+H)+] 256.

Provenance & Evidence