Synthesis
The general procedure for the synthesis of tert-butyl (S)-(piperidin-3-ylmethyl)carbamate from 3-Boc-aminomethylpiperidine is as follows:Example 4 Synthesis of (3S)-N-(tert-butoxycarbonyl)-3-aminomethylpiperidine (Compound 5): N-(tert-butoxycarbonyl)-3-aminomethylpiperidine (10 g, 47 mmol, 1 equiv), (-)-O,O' -di-β-tosyl-L-tartaric acid (15.52 g, 47 mmol, 1 eq.) were mixed with dry methanol (100 ml) and slowly heated to reflux to form a homogeneous solution. The reaction mixture was cooled to room temperature and stirred for 5-6 hours. The resulting white solid was filtered and washed with a minimal amount of anhydrous methanol. The crude product was purified by recrystallization from methanol. The resulting compound was suspended in distilled water (25 ml) and cooled to 0°C. 10% sodium carbonate solution (100 ml) was added in batches until the reaction mixture was basic and stirring was continued for 10 minutes. The reaction mixture was extracted with ethyl acetate (5 x 50 ml), the organic layer was separated and concentrated under reduced pressure after drying to give the target compound 3. Yield: 3.28 g (65%). [α]D: +11.03 (c=0.10, methanol). Melting point: 64-66°C. IR (pure): 3360, 2972, 1703, 1519, 1455, 1365, 1255, 1172 cm-1. 1H NMR (CDCl3, 300MHz) δ: 1.01-1.21 (m, 2H, H-4); 1.39 (s, 9H, -OC(CH3)3); 1.57- 1.72 (m, 3H, H-3, H-5); 2.20-2.31 (m, 1H, CHaNHBoc); 2.49-2.56 (m, 1H, CHbNHBoc); 2.90-3.03 (m, 4H, H-2, H-4); 4.77 (brs, 1H, NH).13C NMR (CDCl3, 300MHz) δ : 26.56, 29.03, 29.58, 38.44, 44.99, 47.46, 51.16, 79.73, 156.72. FAB MS (m/z): 215 (M+1, 114).
