Synthesis
N-[(1,1-dimethylethoxy)carbonyl]-L-valyl-L-proline (Compound 2) was prepared from compound (CAS: 38017-75-3) by alkali hydrolysis reaction using a modified literature method. The procedure was as follows: compound 1 (1.372 g, 4.18 mmol) was dissolved in a solvent mixture of tetrahydrofuran (THF) and water (3:1 volume ratio, total volume of 80 mL, wherein 60 mL of THF and 20 mL of water). Subsequently, lithium hydroxide monohydrate (LiOH-H2O, 0.878 g, 20.89 mmol) was added and the reaction mixture was stirred at room temperature for 2 hours. Upon completion of the reaction, the reaction was acidified with 0.5 M hydrochloric acid (50 mL) to quench the reaction, followed by extraction with ethyl acetate (EtOAc, 4 × 60 mL). The organic phases were combined, washed with saturated saline (1 × 100 mL) and dried over anhydrous magnesium sulfate (MgSO4). The solvent was removed by evaporation under reduced pressure to give a white solid product (1.186 g, 90% yield). The structure of the product was confirmed by 1H NMR, 13C NMR and ESI-MS: 1H NMR (400 MHz, CDCl3) δ 9.37 (br s, 1H, COOH), 5.46 (d, J = 9.4 Hz, 1H, NH), 4.55 (dd, J = 8.1, 4.8 Hz, 1H, Pro-αH), 4.26 (dd, J = 9.4, 6.4, 6.4, 6.4), 1H, Pro-αH), 1H, Pro-αH, 1H, Pro-αH), 1H, Pro-αH, Pro-αH, Pro-αH, Pro-αH. J = 9.4, 6.8 Hz, 1H, Val-αH), 3.83-3.59 (m, 2H, Pro-δH), 2.25-1.86 (m, 5H, Pro-βH, Pro-γH, Val-βH), 1.40 (s, 9H, tBu), 0.98 (d, J = 6.7 Hz, 3H, Val-γH), 0.91 (d , J = 6.7 Hz, 3H, Val-γH); 13C NMR (101 MHz, CDCl3) δ 174.5, 172.4, 155.9, 79.6, 59.1, 57.0, 47.5, 31.2, 28.5, 28.3, 24.8, 19.2, 17.6; ESI-MS (m/z): [M+Na]+ calculated for C15H26N2NaO5 337.1739, found 337.1734.
References
[1] Tetrahedron, 2018, vol. 74, # 12, p. 1184 - 1190
[2] Journal of Organic Chemistry, 2003, vol. 68, # 12, p. 5006 - 5008
[3] Recueil: Journal of the Royal Netherlands Chemical Society, 1980, vol. 99, # 4, p. 124 - 130
[4] Polish Journal of Chemistry, 1988, vol. 62, # 4-6, p. 457 - 464
[5] Bollettino Chimico Farmaceutico, 1999, vol. 138, # 4, p. 160 - 164
![L-Proline, N-[(1,1-dimethylethoxy)carbonyl]-L-valyl-, methyl ester](/CAS/20180808/GIF/38017-75-3.gif)
