Purification of Rapamycin Derivatives Using Temperature Induced Phase Separation

A method for obtaining a purified, solid compound having a structure according to Formula I:

• wherein R1 is Ra—(O)d—Rb, wherein Ra is C1-5alkylene, Rb is C1-5alkyl or C1-5alkylene-OH, and the subscript d is an integer selected from 0-1;
• the method comprising:
• a) forming a mixture consisting essentially of a crude compound having a structure according to Formula I and a non-polar organic solvent under conditions sufficient to dissolve the compound, wherein the dielectric constant of the non-polar organic solvent is less than about 5, wherein the crude compound contains at least 50% of a compound of Formula I by weight, and wherein forming the mixture comprises heating the mixture to reflux;
• b) solidifying at least a portion of the compound having the structure according to Formula I, wherein solidifying a portion of the compound comprises cooling the mixture;
• and
• c) separating at least a portion of the solidified compound from the solvent in the mixture;
• thereby obtaining the purified, solid compound.