Synthesis
Example 1: Synthesis of (R)-(-)-5-oxo-2-tetrahydrofuran carboxylic acid (2)
1. To a mixed solution of D-glutamic acid (1 , 25 g, 170 mmol) in water (67 mL) and concentrated hydrochloric acid (35 mL) was slowly added a solution of NaNO2 (17.5 g, 253.6 mmol) in water (37.5 mL) at 0 °C for 4 hours.
2. After the addition was completed, the reaction mixture was stirred overnight at room temperature to obtain a clarified solution.
3. The solvent was removed by vacuum evaporation and the residue was treated with ethyl acetate (EtOAc, 80 mL) and filtered.
4. The filtrate was dried over anhydrous sodium sulfate (Na2SO4) and subsequently concentrated.
5. The concentrated residue was crystallized from a solvent mixture of ethyl acetate/benzene/hexane to afford (R)-(-)-5-oxo-2-tetrahydrofuran carboxylic acid (2) as a white crystalline solid (12.63 g, 57% yield).
Product Characterization:
- Melting point: 71-73°C
- 1H NMR (400 MHz, CD3OD): δ 4.20 (m, 1H, CHO), 1.8-2.3 (m, 4H, CH2CH2).
References
[1] Tetrahedron, 2006, vol. 62, # 37, p. 8687 - 8695
[2] Tetrahedron: Asymmetry, 1993, vol. 4, # 6, p. 1391 - 1396
[3] Organic Letters, 2014, vol. 16, # 16, p. 4336 - 4339
[4] Pharmazie, 1995, vol. 50, # 1, p. 15 - 21
[5] Patent: US2004/67877, 2004, A1
