(S)-Tert-butyl (piperidin-3-ylmethyl)carbamate synthesis

Yield: 65%

Reaction Conditions:

Stage #1:tert-butyl (piperidin-3-ylmethyl)carbamate with (-)-di-p-toluoyl-L-tartaric acid in methanolReflux;Resolution of racemate;
Stage #2: with sodium carbonate in water at 0;Resolution of racemate;

Steps:

4
Example 4Synthesis of (3S)-N-(t-butoxycarbonyl)-3-aminomethyl-piperidine (compound 5); N-(t-butoxycarbonyl)-3-aminomethyl piperidine (10 g, 1eq, 47 mmol), (-)-O, O -Di-p-tolouyl- L-tartaric acid (15.52, 1eq, 47 mmol) and dry methanol (100 ml) were mixed and heated slowly to refluxing to just to get a uniform solution. The reaction mixture was cooled to room temperature and stirred at this temperature for 5-6 hours. White solid formed was filtered out and washed with minimum quantity of dry methanol. The crude solid was recrystallized from methanol. The compound was suspended in distilled water (25 ml) and cooed to 0 °C. 10% solution of sodium carbonate solution (100 ml) was then added portion wise, until basic, with stirring for 10 min. The reaction mixture was extracted with ethyl acetate (5 x 50 ml). The organic layer was separated, dried and concentrated under reduced pressure to obtain the compound of formula 3.Yield: 3.28g, 65 %^{L J} D : + 11.03 (c = 0.10; Methanol)MP: 64-66 °CIR (Neat):3360, 2972, 1703, 1519, 1455, 1365, 1255, 1172 cm^"1 H NMR (CDCI₃, 300 MHz)δ 1.01 -1.21 (m, 2H, H-4); 1.39 (s, 9H, -0-C(CH₃)₃); 1.57-1.72 (m, 3H, H-3, H-5); 2.20-2.31 (m, 1 H, CH_aNHBoc); 2.49-2.56 (m, 1 H, CH_bNHBoc); 2.90-3.03 (m, 4H, H-2, H-4); 4.77(brs, 1 H, NH)¹³C NMR(CDCI₃, 300 MHz)26.56, 29.03, 29.58, 38.44, 44.99, 47.46, 51.16, 79.73, 156.72FAB MS (m/z):215(M+1 f , 1 14

References:

COUNCIL OF SCIENTIFIC & INDUSTRIAL RESEARCH;DIKSHIT, Dinesh, Kumar;DIKSHIT, Madhu;SIDDIQUI, Tanveer, Irshad;KUMAR, Anil;BHATTA, Rabi, Sankar;JAIN, Girish, Kumar;BARTHWAL, Manoj, Kumar;MISRA, Ankita;KHANNA, Vivek;PRAKASH, Prem;JAIN, Manish;SINGH, Vishal;GUPTA, Varsha;DWIVEDI, Anil, Kumar WO2012/104866, 2012, A1 Location in patent:Page/Page column 17-18