Patent ID: 6495701
Filing Date: 2002-12-17
Classification: C07C,C07D

Abstract:
A process for preparing a compound of the formula (1): wherein R1 is lower alkyl or benzyl; R2 is hydrogen, halogen or hydroxyl; *1 is an asymmetric carbon atom; and A is one of the following groups: wherein X is NH, O or S; R6 is hydrogen, hydroxyl, amino or acetylamino; and *2 is an asymmetric carbon atom when R6 is not hydrogen, said process comprising:(a) i) reacting a compound of the formula (4): â€ƒwherein R1 is as defined above; R21 is hydrogen, halogen, hydroxyl or protected hydroxyl; R3 is an amino-protecting group or hydrogen, with a compound of the formula (12): â€ƒwherein R4 is an amino-protecting group; and Aâ€² is one of the following groups: â€ƒwherein X is NH, O or S; R61 is hydrogen, protected hydroxyl, protected amino or an acetylamino group; and *2 is an asymmetric carbon atom when R61 is not hydrogen, to give a compound of the formula (3): â€ƒwherein R1, R21, R3, R4 and Aâ€² are as defined above; or ii) coupling a compound of the formula (4) with a compound of the formula (14): â€ƒwherein R4 is as defined above, to give a compound of the formula (6): â€ƒwherein R1, R21, R3 and R4 are as defined above; or iii) further converting the primary hydroxyl group of the compound of the formula (6) into a leaving group B3 to give a compound of the formula (5): â€ƒwherein R1, R21, R3 and R4 are as defined above, and B3 is a leaving group; or iv) further reacting the resulting compound of the formula (5) with a compound Aâ€²â€”OH wherein Aâ€² is as defined above to give a compound of the formula (3); (b) reducing the resulting compound of any one of the formulae (3), (5) and (6) to give a compound of the formula (2) as follows: i) reducing the compound of the formula (3) to give an amino-alcohol of the formula (2): â€ƒwherein R1, R21, R3, R4 and Aâ€² are as defined above, and *1 is an asymmetric carbon atom; or ii) reducing the compound of the formula (5) to give a compound of the formula (7): â€ƒwherein R1, R21, R3, R4 and B3 are as defined above, and *1 is an asymmetric carbon atom, or reducing the compound of the formula (6) to give a compound of the formula (8): â€ƒwherein R1, R21, R3 and R4 are as defined above, and *1 is an asymmetric carbon atom, and converting the primary hydroxyl group of the resulting compound of the formula (8) into a leaving group B3 to give a compound of the formula (7), then reacting the compound of the formula (7) obtained by either step as set forth above with a compound Aâ€²â€”OH wherein Aâ€² is as defined above to give an amino-alcohol of the formula (2); and (c) simultaneously or sequentially removing the protecting groups of the compound of the formula (2) obtained by any one of processes as set forth above to give a compound of the formula (1).