N-[(3R)-3-Piperidinylmethyl]-carbamic acid 1,1-dimethylethyl ester

142643-29-6

879275-33-9

The general procedure for the synthesis of tert-butyl (R)-[[piperidin-3-yl]methyl]carbamate from 3-Boc-aminomethylpiperidine is as follows:Example 3 Synthesis of (3R)-N-(tert-butoxycarbonyl)-3-aminomethylpiperidine (Compound 4); 4N-(tert-butoxycarbonyl)-3-aminomethylpiperidine (10 g, 1 eq, 47 mmol) was mixed with (+)-0,. 0'-di-p-tolyl-D-tartaric acid (15.52 g, 1 eq, 47 mmol) were mixed in dry methanol (100 ml) and slowly heated to reflux to form a solution. The solution was cooled to room temperature and stirred at that temperature for 5-6 h. A white suspension was obtained, filtered and washed with a minimal amount of anhydrous methanol. The crude salt was recrystallized once by methanol and the resulting salt was suspended in distilled water (25 ml) and cooled to 0°C. Subsequently 10% sodium carbonate solution (100 ml) was added in batches until the suspension became strongly basic. The reaction mixture was continued to be stirred for 10 min and extracted with ethyl acetate (5 x 50 ml). The organic layers were combined, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give compound 4. Yield: 3.2 g in 62% yield. [α]D °C: -8.97 (c=1.0; methanol). Melting point: 64-66°C. IR (Neat): 3362, 2970, 1703, 1520, 1454, 1365, 1172 cm-1. 1H NMR (CDCl3, 300MHz) δ 1.00-1.22 (m, 2H, H-4); 1.40 (s, 9H, -O-C(CH3)3); 1.57-1.72 (m, 3H, H-3, H-5); 2.21-2.32 (m, 1H, CHaNHBoc); 2.44-2.57 (m, 1H, CHbNHBoc); 2.92-3.05 (m, 4H, H-2, H-4); 4.72 (brs, 1H, NH).13C NMR (CDCl3, 300MHz) 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]+.