Process for the preparation of tert-butyl 4-((2s,5r)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamido)piperidine-1-carboxylate and analogs thereof

A process for preparing a compound of Formula I:

• or a pharmaceutically acceptable salt thereof;
• comprising:
• (a) reacting a compound of Formula (II):
• with a compound of formula (X)
• and a base to obtain a compound of Formula (III) or (IV), or a mixture thereof;
• (b) treating the compound of formula (III) or (IV), or the mixture thereof, with phosgene or a phosgene equivalent to obtain a compound of formula (V) or (VI), or a mixture thereof
• (c) treating the compound of formula (V) or (VI), or a mixture thererof, with a hydrolysis reagent to obtain the compound of formula (I);
• wherein
• Z is O or —NR5;
• k is an integer equal to 0, 1, or 2;
• R2 and R3 are defined as follows:
• (a) R2 is H, C1-6 alkyl, —O—C1-6 alkyl, —O-Si-(C1-6 alkyl)3, or
• —O—Si—(C1-6 alkyl)(phenyl)2, and
• each R3 is H or C1-6 alkyl;
• or
• (b) alternatively and with the proviso that k is 1 or 2, R2 and the R3 adjacent to R2 together with the carbon atoms to which each is attached form C5-7 cycloalkyl which is optionally substituted with from 1 to 3 substituents each of which is independently C1-6 alkyl, —C1-6 alkyl, —O—Si—(C1-6 alkyl)3, or
• —O—Si—(C1-6 alkyl)(phenyl)2;
• and any other R3 is H or C1-6 alkyl;
• R5 is H, C1-6 alkyl, C3-6cycloalkyl, aryl, —C1-6alkyl-aryl, heteroaryl, —C1-6alkyl-heteroaryl, or
• R6 and R8 are independently H, C1-3 alkyl, —O—C1-3 alkyl, or —N—(C1-3 alkyl)2;
• each R7 and R9 is independently H or C1-6 alkyl;
• PG2 is an amine protecting group selected from carbamates, benzylamines, sulfonamides and amides;
• R10 is benzyl or allyl, wherein the benzyl or allyl is optionally substituted with C1-6 alkyl, C1-6 alkoxy, fluoro, or —NO2;
• R11 and R12 are C1-6 alkyl or aryl;
• or
• R11 and R12 together with the silane to which they are attached form a 4- to 6-membered saturated monocyclic ring containing 0 or 1 heteroatoms selected from N and O, which is optionally fused with 1 or 2 aromatic rings each optionally containing 0 or 1 heteroatoms selected from N and O;
• R13 is a leaving group;
• p is 0, 1, or 2;
• q is 0, 1, or 2;
• p+q=0, 1, 2, or 3;
• and
• Ra and Rb are halo.