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 diisopropylethyl amine (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 in vacuo. The residue is partitioned between ethyl acetate and 10% aqueous HCl (1.20 liter each). The layers are shaken, the organic layer separated and washed with 10% HCl and brine (800 ml each). The organic layer is dried over MgSO4 and filtered. As the solvent is removed in vacuo a solid began to precipitate out (˜¼ 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, 1 H); Anal. Calcd for C11H11FN2O3: C, 55.46; H, 4.65; N, 11.76. Found: C, 55.34; H, 4.60; N, 11.69.

Provenance & Evidence