The amino group conservation the 4 hydroxy proline or the refinement modulo null of the 4 hydroxy proline

摘要

PURPOSE:To provide a purification method of an amino group-protected 4- hydroxyproline or 4-hydroxyproline derivative capable of purifying in a short time and readily dissolving the product in an organic solvent. CONSTITUTION:4-Hydroxy-L-proline is dissolved in distilled water and a solution of 9-fluorenylmetyl-N-succinimidyl carbonate in acetonitrile is added thereto. Triethylamine is added to the solution little by little while cooling the solution with ice water and the mixture is further stirred at ambient temperature. After, distilled water and sodium chloride are added thereto, ether is added thereto and these components are mixed by shaking and a water layer is separated and its pH is controlled to =2. Ether is added to the water layer and these components are shaken and mixed and an ether layer is separated and sufficient amount of anhydrous magnesium sulfate is added to the ether layer and the layer is allowed to stand one night. The resultant solid is collected by filtration and cleaned with dilute hydrochloric acid and water is replaced with acetonitrile while filtrating under reduced pressure. The solid is dried under reduced pressure to provide a reaction product expressed by the formula (R is H, lower alkyl or aryl).