Synthesis of cephalosporin compounds

A process for preparing a compound of the formula (II), or a salt thereof:

• comprising the step of admixing a compound of formula (III), or a salt thereof,
• with a nucleophile (Nuc)
• in the presence of reagents comprising:
• (a) a palladium source;
• and
• (b) a palladium-binding ligand;
• to form a compound of formula (II), or a salt thereof,
• wherein:
• Nuc is R4-M, wherein M is H, a metal cation, a non-metal cation, or a lone pair of electrons;
• R4 is the radical resulting from addition of Nuc;
• LG is a leaving group selected from the group consisting of halo, −O(C═O)N(R18)2, −O(C═O)OR18 and −OC(O)R18, wherein R18 is independently in each instance selected from the group consisting of C1-6 alkyl and haloalkyl;
• R1 is selected from the group consisting of:
• Y is selected from the group consisting of:
• R2 is hydrogen;
• R3 is an oxygen protecting group;
• Z′ is an oxygen protecting group;
• R′ is an oxygen protecting group;
• and
• R″ is a nitrogen protecting group.

A process for preparing a compound of formula (IIIa):

• or a salt thereof, comprising the step of admixing a compound of formula (IXa)
• or a salt thereof,
• with a compound of formula (X):
• in the presence of reagents comprising:
• (a) a palladium source;
• and
• (b) a palladium-binding ligand;
• to form a compound of formula (VIIIa), or a salt thereof
• wherein:
• is a pharmaceutically acceptable anion;
• LG is halo, —O(C═O)N(R18)2, —O(C═O)OR18 or —OC(O)R18, wherein R18 is selected from the group consisting of C1-6 alkyl and haloalkyl;
• R3 is an oxygen protecting group;
• R5 is a nitrogen protecting group;
• and
• R6 is a nitrogen protecting group.