Patent ID: 7153957

Claim:
A process for preparing a 42-ester of rapamycin, which comprises: (a) acylating a rapamycin 31-silyl ether with a compound of formula HOOC.CR 7 R 8 R 9 or a mixed 2,4,6-trichlorobenzoyl anhydride thereof, wherein: R 7 is hydrogen, alkyl of 1–6 carbon atoms, alkenyl of 2–7 carbon atoms, alkynyl of 2–7 carbon atoms, —(CR 12 R 13 ) f OR 10 , —CF 3 , —F, or —CO 2 R 10 ; R 10 is hydrogen, alkyl of 1–6 carbon atoms, alkenyl of 2–7 carbon atoms, alkynyl of 2–7 carbon atoms, triphenylmethyl, benzyl, alkoxymethyl of 2–7 carbon atoms, chloroethyl, or tetrahydropyranyl; R 8 and R 9 are taken together to form X; X is a 2-phenyl-1,3,2-dioxaborinan-5-yl or a 2-phenyl-1,3,2-dioxaborinan-4-yl, wherein the phenyl may be optionally substituted; R 12 and R 13 are each, independently, hydrogen, alkyl of 1–6 carbon atoms, alkenyl of 2–7 carbon atoms, alkynyl of 2–7 carbon atoms, trifluoromethyl, or —F; and f=0–6; to give a 42-ester boronate 31-silyl ether of rapamycin; (b) selectively hydrolyzing the 42-ester boronate 31-silyl ether in mild acidic conditions to provide a rapamycin 42-ester boronate; and (c) treating the rapamycin 42-ester boronate with a suitable diol to provide a 42-ester of rapamycin.