Piperidin-4-ol → tert-Butyl 3-(4-hydroxypiperidin-1-yl)azetidine-1-carboxylate

Participants

Reaction Steps

A 10 mL round-bottomed flask was charged with a solution of 3-oxoazetidine-1-carboxylic acid tert-butyl ester (1 g, 5.84 mmol), 4-hydroxypiperidine (0.65 g, 6.42 mmol) and 4 Å molecular sieves (10 g) in DCE (50 mL). The reaction mixture was stirred for 4 h at room temperature. Sodium triacetoxyborohydride (2.48 g, 11.68 mmol) was added and the reaction mixture was stirred for 18 h at room temperature. The suspension was filtered through Celite and the filtrate was concentrated in vacuo. The residue was purified by flash chromatography (Si—PPC, EtOAc:cyclohexane, gradient 0:100 to 100:0) to give 3-(4-Hydroxypiperidin-1-yl)azetidine-1-carboxylic acid tert-butyl ester as a colourless oil (0.34 g, 23%). 1H NMR (CDCl3, 400 MHz) δ 3.92 (t, J=7.8 Hz, 2 H); 3.87-3.72 (m, 3 H); 3.07 (m, 1 H); 2.68-2.63 (m, 2 H); 2.09-2.03 (m, 2 H); 1.96-1.91 (m, 2 H); 1.69-1.55 (m, 2 H); 1.43 (s, 9 H).

Provenance & Evidence