tert-Butyl piperazine-1-carboxylate → Tert-butyl 4-(oxetan-3-YL)piperazine-1-carboxylate

Participants

Reaction Steps

A solution of piperazine-1-carboxylic acid tert-butyl ester (1.56 g, 8.38 mmol) and oxetan-3-one (500 mg, 6.94 mmol) DCE (60 mL) was stirred at ambient temperature for 90 min. Sodium triacetoxyborohydride (2.34 g, 11.04 mmol) was added and the mixture stirred for 17 h, then loaded onto an Isolute® SCX-2 cartridge (25 g). The cartridge was then washed with methanol and the desired product was subsequently eluted using 2 M NH3 in MeOH. The product was collected and concentrated in vacuo. The resultant residue was purified by flash chromatography (Si—PPC, DCM:MeOH; 100:0 to 99:1 to 98:2) to afford 4-Oxetan-3-ylpiperazine-1-carboxylic acid tert-butyl ester as a white solid (1.0 g, 59%). 1H NMR (CDCl3, 400 MHz) δ 4.69-4.58 (m, 4 H); 3.51-3.44 (m, 5 H); 2.27 (m, 4 H) and 1.46 (s, 9 H).

Provenance & Evidence