Monohydrate solvates of loracarbef

A process for the preparation of mono-N, N-dimethylacetamide monohydrate solvate of loracarbef of Formula II-A,

• comprising mixing a compound of Formula III,
• wherein R1 is hydrogen, trihalo (C1-C4 alkyl), C1-C4 alkyl, C1-C4 substituted alkyl, C1-C4 alkoxy, C1-C4 substituted alkoxy, C1-C6 alkylthio, C1-C6 substituted alkylthio, methoxy methyl, carbamoyloxy methyl, acetoxymethyl, C2-C6 alkenyl,
• C2-C6 substituted alkenyl, or halogen such as bromo, chloro, fluoro, and iodo;
• and
• R2 is a carboxy-protecting group,
• with N,N-dimethylacetamide and a base to form a free amine of the compound of formula IV, and
• reacting the compound of Formula IV with an acylating agent of Formula V,
• wherein R3 is an amino protecting group and L is a leaving group.

A process for the preparation of mono N-methylpyrrolidone monohydrate solvate of loracarbef of Formula II-B,

• comprising mixing a compound of Formula III,
• wherein R1 is hydrogen, trihalo (C1-C4 alkyl), C1-C4 alkyl, C1-C4 substituted alkyl, C1-C4 alkoxy, C1-C4 substituted aLkoxy, C1-C6 aLkylthio, C1-C6 substituted alkylthio, methoxy methyl, carbamoyloxy methyl, acetoxymethyl, C2-C6 alkenyl, C2-C6 substituted alkenyl, or halogen such as bromo, chloro, fluoro, and iodo;
• and R2 is a carboxy-protecting group,
• with N-methylpyrrolidone and a base, to form a free amine of the compound of formula IV, and
• reacting the compound of Formula IV with an acylating agent of Formula V,
• wherein R3 is an amino protecting group and L is a leaving group.