Patent ID: 6670477
Filing Date: 2003-12-30
Classification: C07D,Y02P

Abstract:
A process for making enantiomerically enriched 4-piperidinylglycine having the formula (I), said process comprising(a) combining N-protected glycine ester having the formula (II) â€ƒwith 4-piperidone having the formula (III) â€ƒwhereby didehydroamino acid ester is formed having the formula (IV); (b) reducing the didehydroamino acid ester (IV) with hydrogen gas in the presence of a rhodium catalyst selected from the group consisting of (R,R)-BPE-Rh having the formula (A1), (S,S)-BPE-Rh having the formula (A2), (R,R)-DuPHOS-Rh having the formula (B1), (S,S)-DuPHOS-Rh having the formula (B2), and combinations thereof; â€ƒwhereby a protected compound is formed having the formula (V); (c) removing the protecting groups of formula (V), whereby the 4-piperidinylglycine having the formula (I) is formed; wherein R1 is selected from the group consisting of hydrogen and PO(OM)2, wherein M is a phenyl or C1-C8 linear, branched or cyclic alkyl group; R2 is selected from the group consisting of hydrogen, phenyl and a C1-C8 linear, branched or cyclic alkyl group; R3 and R4 are independently selected from the group consisting of hydrogen, phenyl, a C1-C8 linear, branched or cyclic alkyl group, and OR6, wherein R6 is selected from the group consisting of hydrogen, phenyl, benzyl, substituted benzyl, and C1-C8 linear, branched or cyclic alkyl group; R5 is independently selected from the group consisting of a C1-C8 linear, branched or cyclic alkyl group, a C1-C8 linear, branched or cyclic fluoroalkyl group, and combinations thereof; diene is a counter ligand independently selected from the group consisting of cyclooctadiene and norbornadiene; Aâˆ’ is an anion wherein A is independently selected from the group consisting of trifluoromethanesulfonate, tetrafluoroborate, hexafluoroantimonate, and hexafluorophosphate; Xâˆ’ is an anion wherein X is independently a halogen; and â€œ*â€  designates an asymmetric carbon having (R)- or (S)-configuration.