Process for the preparation of protected L-alanine derivatives

A process for the preparation of a compound of formula (I)

• wherein
• PG1 is a nitrogen protecting group;
• R0 is selected from the group consisting of hydrogen, C1-4-alkyl and benzyl;
• R6 is selected from the group consisting of hydrogen and C1-6alkyl;
• R4 is aryl or heteroaryl;
• wherein the aryl or heteroaryl is optionally substituted with one to five substituents independently selected from the group consisting of C1-6alkyl, C1-6alkoxy, arylC1-6alkoxy, arylC1-6alkylcarbonyloxy, heteroarylC1-6alkylcarbonyloxy, heteroaryl, hydroxy, halogen, aminosulfonyl, formylamino, aminocarbonyl, C1-6alkylaminocarbonyl, di(C1-6alkyl)aminocarbonyl, heterocyclylcarbonyl, carboxy, and cyano;
• wherein the C1-6alkyl is optionally substituted with amino, C1-6alkylamino, or (C1-6alkyl)2amino;
• and wherein the aryl portion of arylC1-6alkylcarbonyloxy is optionally substituted with one to four substituents independently selected from the group consisting of C1-6alkyl, C1-6alkoxy, halogen, cyano, amino and hydroxy;
• and pharmaceutically acceptable enantiomers, pharmaceutically acceptable diastereomers, pharmaceutically acceptable racemates and pharmaceutically acceptable salt thereof;
• comprising
• reacting a compound of formula (X), wherein PG1 is a nitrogen protecting group, with zinc;
• in the presence of a source of iodine;
• in a first organic solvent, or a mixture of organic solvents wherein the first organic solvent is non-reactive to the source iodine;
• to yield the corresponding compound of formula (XI);
• reacting the compound of formula (XI) with a compound of formula (XII), wherein LG1 is a leaving group;
• in the presence of a palladium catalyst and phosphine ligand system;
• in a second organic solvent or a mixture of organic solvents;
• to yield the corresponding compound of formula (I).