摘要 |
PROBLEM TO BE SOLVED: To effectively obtain a high-pure nucleic acid derivative by applying a specific treatment to a raw material mixture including an impurity and isolating the precipitated crystal. SOLUTION: A mixture of a nucleic acid derivative of formula I obtained by reacting 2-amino-6-chloroproline with a compound of (1S,2R)-3-oxa-2- oxobicyclo[3.1.0]hexane-1-methanol in which a hydroxyl group is substituted with a leaving group, with a byproduct such as a compound of formula II is suspended in an alcohol solvent such as methanol and ethanol, or the alcohol solvent containing 0-50 vol.% water. Further, any of 1-5 eq. alkali metal hydroxide based on the compound of formula I, an aqueous solution thereof, an alcohol solution thereof, and an alkoxide of the alkali metal is added to the suspension, and the added suspension is reacted at a temperature from 0 deg.C to the reflux temperature of the solvent for 0.5-50 hr. Thereafter, the reaction mixture is cooled to 0-30 deg.C and subjected to an aging of 0.5-50 hr to provide a compound of formula III as a crystal, and the crystal is filtrated to isolate the objective compound of formula III in the method for purifying a nucleic acid derivative. |