Enantio- and stereo specific synthesis of β-amino-α-hydroxy amides
Processes useful for the preparation of a Compound of Formula I: Formula (I). Intermediates useful for the preparation of the compound of Formula I, and processes useful for preparing said intermediates are disclosed.
1. A process for preparing the compound of Formula I
comprising:
1) coupling a bicyclo intermediate of Formula II with an amine intermediate of Formula III in the presence of coupling reagents to obtain the intermediate alcohol of Formula IV:
and
2) oxidizing the intermediate of Formula IV.
2. The process of claim 1 wherein the compounds of Formula II and III are coupled using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide and 1-hydroxybenzotriazole in the presence of N,N-diisopropylethylamine.
3. The process of claim 1 wherein the compound of Formula IV is oxidized with sodium hypochlorite in the presence of a catalytic or stoichiometric amount of 2,2,6,6-tetramethyl-1-piperidinyloxy free radical.
4. A process for preparing the compound of Formula I
comprising:
1) coupling the acid of Formula VI with the secondary amine of Formula VII-1 in a water soluble solvent the presence of coupling agents to obtain the compound of Formula Va:
2) converting the methyl ester of Formula Va to the acid of Formula II:
3) coupling the acid of Formula II with an amine intermediate of Formula III in the presence of coupling reagents to obtain the intermediate alcohol of Formula IV:
and
4) oxidizing the intermediate of Formula IV.
5. The process of claim 4 wherein the compounds of Formula VI and VII are coupled using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide and 1-hydroxybenzotriazole in the presence of N-methylmorpholine in acetonitrile.
6. The process of claim 4 wherein the compounds of Formula II and III are coupled using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide and 1-hydroxybenzotriazole in the presence of N,N-diisopropylethylamine.
7. The process of claim 4 wherein the compound of Formula IV is oxidized with sodium hypochlorite in the presence of a catalytic or stoichiometric amount of 2,2,6,6-tetramethyl-1-piperidinyloxy free radical.