tert-butyl 4-(piperidine-3-carbonyl)piperazine-1-carboxylate synthesis

Yield:-

Reaction Conditions:

with benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate;N-ethyl-N,N-diisopropylamine in N,N-dimethyl-formamide at 20;

Steps:

tert-butyl 4-(thiophen-2-ylcarbonyl)piperazine-1-carboxylate (10e)

General procedure: 1-Boc-piperazine (150 mg, 0.81 mmoles) was dissolved in anhydrous DMF (2 mL) and, under stirring, DIPEA (303 mL, 1.78 mmoles), PyBOP (461 mg, 0.89 mmoles) and 2-thiophenecarboxylic acid (114 mg, 0.89 mmoles) were added at room temperature. After complete conversion of 1-Boc-piperazine monitored by TLC analysis, the solution was diluted with DCM and washed with NaOH 0.5M, brine, HCl 0.1M and brine. Organic phase was dried over Na₂SO₄, filtered and concentrated under reduced pressure. The crude product was purified by chromatographic column (eluent DCM/MeOH = 96/4) to obtain 10e (188 mg, 79% yield).

References:

Giannini, Giuseppe;Battistuzzi, Gianfranco;Vesci, Loredana;Milazzo, Ferdinando M.;De Paolis, Francesca;Barbarino, Marcella;Guglielmi, Mario Berardino;Carollo, Valeria;Gallo, Grazia;Artali, Roberto;Dallavalle, Sabrina [Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,# 2,p. 462 - 466] Location in patent:supporting information