Synthesis
The general procedure for the synthesis of N-BOC-L-norleucine from L-norleucine and di-tert-butyl dicarbonate was as follows: free L-norleucine (400 mg, 3.05 mmol) was dissolved in a solvent mixture of water and THF (8.8 mL:8.8 mL), NaHCO3 (768 mg, 9.15 mmol) was added and di-tert-butyl dicarbonate ( 800 mg, 3.66 mmol). The reaction mixture was stirred at 0 °C for 30 min, then gradually warmed to room temperature and continued to stir overnight. Upon completion of the reaction, water (10 mL) was added to dissolve any precipitate that may have formed. Unreacted di-tert-butyl dicarbonate was removed by three extractions with petroleum ether. N-BOC-L-norleucine in the aqueous phase was acidified to pH ≈ 3 with 1 M NaHSO4 solution and subsequently extracted three times with EtOAc. The organic layers were combined and dried with Na2SO4. The solvent was removed by concentration under reduced pressure to give the clear oily product N-BOC-L-norleucine (573 mg, 81% yield). The product was characterized by 1H NMR (400 MHz, DMSO-d6): δ 12.38 (bs, 1H, COOH), 7.02 (d, J=8.2 Hz, 1H, NH), 3.87-3.78 (m, 1H, CH), 1.69-1.47 (m, 2H, CH2), 1.37 (s, 9H, t-Bu), 1.32- 1.20 (m, 4H, CH2), 0.85 (t, J=7.0Hz, 3H, CH3).
References
[1] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 21, p. 6891 - 6899
[2] Bioorganic and medicinal chemistry letters, 2004, vol. 14, # 1, p. 275 - 278
