Synthesis
General procedure for the synthesis of N-BOC-trans-4-hydroxy-D-proline from di-tert-butyl dicarbonate and L-hydroxyproline:
Step A: Preparation of (4β)-1-Boc-4-hydroxy-L-proline
1. dissolve L-hydroxyproline (5.08 g, 38.77 mmol) in a solvent mixture of 1N NaOH solution (40 mL) and 1,4-dioxane (40 mL).
2. Di-tert-butyl dicarbonate (9.3 g, 42.6 mmol) was added drop-wise to the above solution at 0 °C.
3. The reaction mixture was stirred at room temperature for 8 hours. 4.
4. After completion of the reaction, the mixture was concentrated under vacuum to remove the solvent.
5. The concentrated mixture was acidified with 1N HCl and then extracted with EtOAc.
6. The organic extract was washed with brine, dried over MgSO4 and filtered.
7. Finally, the filtrate was concentrated under vacuum to give N-BOC-trans-4-hydroxy-D-proline (8.84 g, 99% yield).
MS [M + H] = 232 (M + 1).
