Patent ID: 8754207

Claim:
A process for preparing a compound of Formula (I), comprising: (i) reacting 2,2-bis(hydroxymethyl)propionic acid of Formula (A), with a suitable ketal of Formula (IIa) in the presence of a suitable acid catalyst to obtain a compound of Formula (IIb), wherein, each R is a (C 1 -C 3 )alkyl group; and each R 1 and R 2 independently represents a (C 6 -C 10 )aryl group, or the R 1 and R 2 together with the carbon atom to which they are attached form a saturated or unsaturated fused or bridged (C 6 -C 14 ) bicyclic or tricyclic ring structure which optionally may be substituted with at least one member selected from the group consisting of halogen, hydroxyl, (C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxyl and halo(C 1 -C 4 )alkyl; (ii) reacting the compound of Formula (IIb) obtained from step (i) with one or more suitable acylating agents in the presence of one or more suitable bases to form a mixed anhydride compound of Formula (IIc) wherein R 1 and R 2 are as defined above; (iii) reacting the compound of Formula (IIc) obtained from step (ii) with rapamycin or 31-protected rapamycin in the presence of one or more suitable bases to give a suitably protected 42-ester rapamycin compound of Formula (IId) wherein R 1 and R 2 are as defined above and P is either H or a suitable protecting group; and (iv) hydrolyzing the compound of Formula (IId) obtained from step (iii) with a suitable acid to obtain the compound of Formula (I).