Ethyl chloroformate → 5-Fluoro-3H-spiro[benzofuran-2,4'-piperidine]

Participants

Reaction Steps

Ethyl chloroformate (65.6 mg, 0.604 mmol) was added to a solution of 1′-benzyl-5-fluoro-3H-spiro[1-benzofuran-2,4′-piperidine] (150 mg, 0.504 mmol) in toluene (2 mL) and the mixture was refluxed over night, cooled to room temperature, diluted by addition of toluene (10 mL), washed successively with saturated aqueous NaHCO3 solution and water. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo. The residue was dissolved in ethanol (3.5 mL), aqueous KOH (800 mg, KOH in 0.8 mL H2O) was added and the mixture was refluxed over night, cooled to room temperature, ethanol was removed in vacuo. Aqueous layer was extracted with diethyl ether. Combined ether layer is was washed with 3N aqueous HCl. Aqueous layer was adjusted to pH 10 by addition of aqueous 3N NaOH. The basic solution was extracted with ethyl acetate. Combined organic layer was washed with water, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by HPLC (10-55% CH3CN in H2O, 0.1% NH4OH) to give the title compound (49 mg). 1H-NMR (CD3OD, 400 MHz): δ 6.92-6.87 (m, 1H); 6.81-6.75 (m, 1H); 6.64 (dd, J=4.2, 8.7 Hz, 1H); 3.08-2.98 (m, 4H); 2.89-2.81 (m, 2H); 1.91-1.83 (m, 2H); 1.78-1.69 (m, 2H).

Provenance & Evidence