Citric Acid → (2S,4R)-1-(2-{[(benzyloxy)carbonyl]amino}acetyl)-4-hydroxypyrrolidine-2-carboxylic acid

Participants

Reaction Steps

3,4-Dehydroproline 1 (0.011 g, 0.097 mmol) and sodium hydrogen carbonate (0.0082 g, 0.097 mmol) were dissolved in water (1 cm3). A solution of N-tert-butyloxycarbonylglycine N-hydroxysuccinimide 2 (0.024 g, 0.088 mmol) in dioxane (1 cm3) was added dropwise and stirred overnight. The reaction mixture was diluted with water, acidified with solid citric acid and extracted with dichloromethane (3×). The combined organic layers were dried (MgSO4), filtered and the solvent removed to afford crude acid 3 (0.0242 g, ca. 100%) that was used without further purification. Acid 3 was shown to be a 75:25 trans:cis mixture of conformers by 1H NMR analysis (the ratio was estimated from the integration of the Proα protons at δ 5.21 and 5.13 of the major and minor conformers respectively): δH (300 MHz; CDCl3; Me4Si) 1.411 [2.25H, s, C(CH3)3], 1.42 [6.75H, s, C(CH3)3], 3.83-4.08 (2H, m, Glyα-H2), 4.25-4.45 (2H, m, Proδ-H2), 5.13* (0.25H, br d, J 2.8, Pros-H), 5.21 (0.75H, br d, J 3.1, Proα-H), 5.55-5.80 (2H, br m, O—H and N—H) and 5.86-6.02 (2H, m, Proβ-H and Proγ-H).

Provenance & Evidence