[Synthesis]
GENERAL STEPS: L-isoleucine (1.31 g, 10 mmol, 1.0 equiv) was dissolved in 20.5 mL of 1 M NaOH solution and cooled in an ice bath. Di-tert-butyl dicarbonate (Boc2O, 2.62 g, 12 mmol, 1.2 equiv) dissolved in 7 mL of dioxane was added slowly. The reaction mixture was stirred at ambient temperature for 24 hours. Subsequently, the pH of the reaction solution was adjusted to 10 with 1 M NaOH and ether was added for phase separation. The aqueous phase was acidified to pH 2 with 1 M HCl and extracted with ethyl acetate (EtOAc). The combined organic phases were washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to give BOC-L-isoleucine as a colorless oil (2.20 g, 95% yield).
IR (cm-1): 3292 (w), 2967 (m), 2934 (w), 2880 (w), 1713 (s), 1661 (m), 1504 (m), 1465 (w), 1394 (m), 1368 (s), 1242 (m), 1159 (s), 1121 (m), 1046 (m), 1019 (w), 857 (w), 778 857 (w), 778 (w), 657 (w).
1H NMR (500 MHz, CDCl3) δ: 0.94 (t, J = 7.3 Hz, 3H, H-6), 0.98 (d, J = 7 Hz, 3H, H-4), 1.15-1.29 (m, 1H, H-5a), 1.46 (s, 9H, H-9/10/11), 1.46-1.54 (m, partially overlapped, 1H, H-5b), 1.83-1.99 (m, 1H, H-3), 4.30 (dd, J = 8.9, 4.6 Hz, 1H, H-2), 5.02 (d, J = 8.9 Hz, 1H, NH).
13C NMR (125 MHz, CDCl3) δ: 11.8 (C-6), 15.7 (C-4), 25.0 (C-5), 28.5 (C-9/10/11), 37.9 (C-3), 58.0 (C-2), 80.2 (C-8), 155.9 (C-7), 177.2 (C-1).
HRMS (ESI) m/z: [M-H]- calcd for C11H20NO4 230.13868, found 230.13926.
[α]20D +3.6 (c 2.00, CH3OH) (Lit [3]: [α]25D +3.8 (c 1.01, CH3OH)). |
[References]
[1] Tetrahedron Letters, 2005, vol. 46, # 38, p. 6537 - 6540
[2] Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 17, p. 6340 - 6350
[3] Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 14, p. 3573 - 3586
[4] Tetrahedron, 1992, vol. 48, # 37, p. 8007 - 8022
[5] Tetrahedron, 2006, vol. 62, # 31, p. 7274 - 7283 |