Sodium Carbonate → 1-Ethoxycarbonyl-4-(4-fluoro-2-nitroanilino)piperidine

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A solution of ethyl 4-amino-1-piperidine carboxylate (9.0 g, 52 mmol.) and 2-chloro-5-fluoronitrobenzene (10.3 g, 58 mmol.) in cyclohexanol (30 mL) containing powdered sodium carbonate (6.1 g, 57 mmol.) was refluxed (>160° C.) for 30 hours or until no further reaction was indicated by tlc (30% EtOAc/hexane). (Alternatively, 2,5-difluoro-nitrobenzene can be used in place of the 2-chloro-5-fluoronitro-benzene). The deep reddish reaction mixture was cooled and diluted with EtOAc. This solution was washed with dil. aq. HCl (3×), water, and then the organic layer dried (anhydrous Na2SO4) and the solvent evaporated to give a red oil. This oil was flash chromatographed on a column of silica gel and the product eluted with a 10-25% EtOAc/hexane gradient. The appropriate fractions were combined, the solvents evaporated, and the residue triturated with 10% Et2O/hexane to give 1-ethoxycarbonyl-4-(4-fluoro-2-nitroanilino)-piperidine as a bright reddish-orange solid, mp: 115-116° C., which was used without further purification.

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