Diisopropylethylamine → 1-(2-Fluoro-4-nitrophenyl)piperidin-4-one

Participants

Reaction Conditions

Reaction Steps

To a stirring solution of 4-piperidone monohydrate hydrochloride (258.7 g, 1.68 mol) and diisopropylethylamine (590 ml, 3.39 mol) in acetonitrile (2.5 liter) is added 3,4-difluoronitrobenzene (186.3 ml, 1.68 mol). The mixture is heated to 80° C. and stirred overnight. The solvent is cooled to ambient temperature and removed under reduced pressure. The residue is partitioned between ethyl acetate and 10% aqueous HCl (1.20 liter each). The layers are shaken, and the organic layer is separated and washed with 10% HCl and saline (800 ml each). The organic layer is dried over MgSO4 and filtered. As the solvent is removed under reduced pressure a solid begins to precipitate out (˜1/4 volume). The resulting slurry is cooled to 0-5° C. and filtered to afford 333.7 g of the title compound, 1H NMR (400 MHz, CDCl3) δ 2.65 (m, 4 H), 3.65 (m, 4 H), 6.98 (m, 1 H), 7.26 (s, 1 H), 8.00 (m, 1H).

Provenance & Evidence