Process for the synthesis of azetidinones

A process for preparing a compound represented by the formula

• comprising:
• reacting a chiral alcohol of formula V, an imine of formula VI and a hydroxy protecting agent, then condensing the hydroxy-protected compounds to obtain a β-(substituted-amino)amide of formula VII, wherein X is —O—, —S— or —N(C1-C6 alkyl);
• Y is ═O or ═S;
• and R1 is C1-C6 alkyl, phenyl, naphthyl, substituted phenyl, substituted naphthyl, C1-C6 alkoxycarbonyl or benzyl, wherein the substituents on phenyl and naphthyl are 1-3 substituents selected from the group consisting of C1-C6 alkyl, phenyl and benzyl;
• and wherein Prot is a hydroxy protecting group:
• cyclizing the β-(substituted-amino)amide of formula VII with a silylating agent and a fluoride ion catalyst cyclizing agent to obtain the compound of formula VIII:
• removing the hydroxy protecting groups.

A process for preparing a compound represented by the formula

• comprising cyclizing a β-(substituted-amino)amide of formula VII,
• wherein X is —O—, —S— or —N(C1-C6 alkyl);
• Y is ═O or ═S;
• and R1 is C1-C6 alkyl, phenyl, naphthyl, substituted phenyl, substituted naphthyl, C1-C6 alkoxycarbonyl or benzyl, wherein the substituents on phenyl and naphthyl are 1-3 substituents selected from the group consisting of C1-C6 alkyl, phenyl and benzyl;
• and wherein Prot is a hydroxy protecting group, with a silylating agent and a fluoride ion catalyst cyclizing agent to obtain the compound of formula VIII:
• (e) removing the hydroxy protecting groups.

A process for preparing a β-(substituted-amino)amide of the formula

• wherein X is —O—, —S— or —N(C1-C6 alkyl);
• Y is ═O or ═S;
• and R1 is C1-C6 alkyl, phenyl, naphthyl, substituted phenyl, substituted naphthyl, C1-C6 alkoxycarbonyl or benzyl, wherein the substituents on phenyl and naphthyl are 1-3 substituents selected from the group consisting of C1-C6 alkyl, phenyl and benzyl;
• and wherein Prot is a hydroxy protecting group, comprising reacting a chiral alcohol of formula V,
• an imine of formula VI
• and a hydroxy protecting agent, then condensing the hydroxy-protected compounds to obtain the β-(substituted-amino)amide.

A process for preparing a compound of the formula

• wherein Prot is a hydroxy protecting group, comprising cyclizing β-(substituted-amino)amide of the formula
• wherein X is —O—, —S— or —N(C1-C6 alkyl);
• Y is ═O or ═S;
• and R1 is C1-C6 alkyl, phenyl, naphthyl, substituted phenyl, substituted naphthyl, C1-C6 alkoxycarbonyl or benzyl, wherein the substituents on phenyl and naphthyl are 1-3 substituents selected from the group consisting of C1-C6 alkyl, phenyl and benzyl;
• and wherein Prot is as defined above, with a silylating agent and a fluoride ion catalyst cyclizing agent.