US 11,680,137 B2
Method for purifying trityl group-containing monodispersed polyethylene glycol
Koichi Ogi, Kawasaki (JP); Takuma Tsubusaki, Kawasaki (JP); and Kohei Yoshimura, Kawasaki (JP)
Assigned to NOF CORPORATION, Tokyo (JP)
Appl. No. 17/42,331
Filed by NOF CORPORATION, Tokyo (JP)
PCT Filed Mar. 26, 2019, PCT No. PCT/JP2019/012867
§ 371(c)(1), (2) Date Sep. 28, 2020,
PCT Pub. No. WO2019/189188, PCT Pub. Date Oct. 3, 2019.
Claims priority of application No. JP2018-063421 (JP), filed on Mar. 29, 2018.
Prior Publication US 2021/0009756 A1, Jan. 14, 2021
Int. Cl. C08G 65/30 (2006.01); C08G 65/324 (2006.01); C08G 65/329 (2006.01); C08G 65/46 (2006.01); C08G 65/48 (2006.01)
CPC C08G 65/30 (2013.01) [C08G 65/324 (2013.01); C08G 65/329 (2013.01); C08G 65/46 (2013.01); C08G 65/48 (2013.01)] 20 Claims
 
1. A method for purifying a trityl group-containing monodispersed polyethylene glycol, which includes, from a mixture containing a trityl group-containing monodispersed polyethylene glycol represented by the following formula (1) and a ditritylated impurity represented by the following formula (2), separating and removing the ditritylated impurity to obtain the trityl group-containing monodispersed polyethylene glycol,
the method comprising: performing steps (A), (B) and (C) in this order:

OG Complex Work Unit Chemistry
wherein, in the formula (1), n is a number of repeating units of an ethylene oxide unit and is 3 or more and 48 or less;

OG Complex Work Unit Chemistry
wherein, in the formula (2), m is a number of repeating units of an ethylene oxide unit and is 3 or more and 92 or less;
Step (A): a step of obtaining a reaction solution containing an ester compound having an ester structure and a carboxyl group by reacting a hydroxyl group of the trityl group-containing monodispersed polyethylene glycol represented by the formula (1) with a dibasic acid anhydride in the following organic solvent II,
Step (B): an extraction step of separating an aqueous layer and an organic layer, partitioning the ditritylated impurity represented by the formula (2) into the organic layer and partitioning the ester compound into the aqueous layer by performing liquid-separation extraction purification using the reaction solution obtained in the step (A), one or more organic solvents selected from the group consisting of the following organic solvents I, II and III, and an aqueous solution having a pH of 3 to 7,
Step (C): a step of performing hydrolysis of the ester compound by adding a base to the aqueous layer to obtain the trityl group-containing monodispersed polyethylene glycol:
Organic solvent I: an alcohol solvent having 3 or less carbon atoms,
Organic solvent II: an aromatic hydrocarbon solvent having 8 or less carbon atoms in total,
Organic solvent III: a saturated aliphatic hydrocarbon solvent having 10 or less carbon atoms in total.