CPC A61K 9/007 (2013.01) [A61K 31/167 (2013.01); A61K 31/485 (2013.01); A61K 47/60 (2017.08); C07C 41/24 (2013.01)] | 11 Claims |
1. A method of preparing a monodisperse oligo(ethylene glycol) reagent composition, comprising:
(i) reacting a halo-terminated oligo(ethylene glycol) having (m) monomer subunits and a C1-C2 alkoxy (methoxy or ethoxy) end-capping group with a first hydroxyl-terminated oligo(ethylene glycol), HO—(CH2CH2O)n—H, having (n) monomer subunits, under conditions effective to displace the halo group from the halo-terminated oligo(ethylene glycol) to thereby form an oligo(ethylene glycol) having (m)+(n) monomer subunits (OEGm+n), wherein reacting the halo-terminated oligo(ethylene glycol) with the first hydroxyl-terminated oligo (ethylene glycol) comprises adding a 1:1 molar ratio of the halo-terminated oligo(ethylene glycol) to the first hydroxyl-terminated oligo (ethylene glycol) in a solution, where halo is selected from chloro, bromo, and iodo;
(ii) converting the terminal hydroxyl group of OEGm+n into a halo group, —X, to form OEGm+n−X; and
(iii) reacting OEGm+n−X with a second hydroxyl-terminated oligo(ethylene glycol) having (n) monomer subunits under conditions effective to displace the halo group of OEGm+n−X to thereby form an oligo(ethylene glycol) having (m)+2(n) monomer subunits (OEGm+2n), wherein reacting the OEGm+n−X with the second hydroxyl-terminated oligo (ethylene glycol) comprises adding a 1:1 molar ratio of OEGm+n−X to the second hydroxyl-terminated oligo (ethylene glycol) in a solution;
where (m) and (n) each independently range from 1-6 in each occurrence, and (OEGm+2n) corresponds to a structure CH3(CH2)0,1O(CH2CH2O)m+2nH, and is present as part of a monodisperse composition of CH3(CH2)0,1O(CH2CH2O)m+2nH.
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