Dichloromethane → 5-Fluorospiro[indoline-3,3'-piperidin]-2-one hydrochloride

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Reaction Steps

t-Butyl 3-(2-bromo-4-fluorophenylcarbamoyl)-1,2,5,6-tetrahydropyridine-1-carboxylate. 2-Bromo-4-fluoroaniline (2.53 g, 13.3 mmol) was dissolved in dichloromethane (30 mL) under N2-atmosphere and trimethylaluminium (2.0 M in hexanes, 8 mL) was added. The solution was stirred during 15 minutes, whereupon a solution of 5,6-dihydro-2H-pyridine-1,3-dicarboxylic acid 1-t-butyl ester 3-methyl ester (3.67 g, 13.3 mmol) in DCM (20 mL) was added. The mixture was refluxed overnight and saturated NaHCO3 was carefully added followed by DCM. The aqueous phase was extracted with DCM. The crude product was purified by chromatography on silica gel using a gradient of toluene to acetonitrile to give the title compound (4.55 g) in 86% yield as an yellow oil. Rf 0.54 (toluene/acetonitrile 3:1). MS(TSP+) m/z calcd for [M+NH4]+: 416, 418, observed: 416, 418.

Provenance & Evidence