Patent ID: 7563888

Claim:
A process for the preparing of diphenylazetidinone derivative of formula (I), wherein: X is OH; R 1 is OH, or OCH 3 ; R 2 is F, CH 2 CH 3 , or CH 2 NHR 4 ; R 3 is H, or F; R 4 is H, CO—(CH 2 —) n CO—R 5 , or CO—(CH 2 —) n NHR 6 ; n is an integers from 4 to 16; R 5 is OH or NH—CH 2 —[CH(OH)—] m CH 2 OH; R 6 is H or CO—[CH(OH)—] m CH 2 OH; and m is an integers from 1 to 5; comprising (a) reacting a compound of formula (II) wherein: Y is H, OH; H, O-acetyl; H, OSi(alkyl) o (aryl) p wherein o and p are independently 0, 1, 2 or 3, and o+p is 3; H, O-tetrahydropyranyl; H, OC(aryl) 3 ; H, OCH 2 Oalkyl; H, OCH(Oalkyl)CH 3 ; or H, OCH 2 aryl; with an imine of formula (III) wherein R 7 is —OH, —OCH 3 or —O—protective group; and R 8 is R 2 , CH 2 N[Si(alkyl) o (aryl) p ]CO 2 CH 2 (C 6 H 5 ), CH 2 N[Si(alkyl) o (aryl) p ]CO 2 tert-butyl, CH 2 N═CH(C 6 H 5 ), CH 2 N═CH(C 6 H 4 -pOCH 3 ), CH 2 N═CH[C 6 H 4 (R 4 )] or to give a compound of formula (IV) (b) hydrolyzing the compound of formula (IV) to give a compound of formula (V) wherein R 9 is H; (c) optionally converting the compound of formula (V) wherein R 9 is H into a compound of formula (V) wherein R 9 is (C 1 -C 4 )alkyl, CO(C 1 -C 4 )alkyl, COO(C 1 -C 4 )alkyl, or SO 2 aryl, or into a corresponding anhydride; (d) cyclizing the compound of formula (V) wherein R 9 is H, (C 1 -C 4 )alkyl, CO(C 1 -C 4 )alkyl, COO(C 1 -C 4 )alkyl, or SO 2 aryl, or the anhydride to give a lactam of formula (VI) (e) optionally deprotecting the compound of formula (VI) wherein Y is H, O-acetyl; H, OSi(alkyl) 0 (aryl) p wherein o and p are independently 0, 1, 2 or 3, and o+p is 3; H, O-tetrahydropyranyl; H, OC(aryl) 3 ; H, OCH 2 Oalkyl; H, OCH(Oalkyl)CH 3 ; or H, OCH 2 aryl; or R 7 is —O—protective group; or R 8 is CH 2 N[Si(alkyl) o (aryl) p]CO 2 CH 2 (C 6 H 5 ), CH 2 N[Si(alkyl) o (aryl) p]CO 2 tert-butyl, CH 2 N═CH(C 6 H 5 ), CH 2 N═CH(C 6 H 4 -pOCH 3 ), CH 2 N═CH[C 6 H 4 (R 4 )] or to give the compound of formula (I) wherein R 2 is F, CH 2 CH 3 , or CH 2 NH 2 ; and (f) optionally reacting the compound of formula (I) wherein R 2 is CH 2 NH 2 with a compounds of formula (XV) or (XVI) to give the compound of the formula (I) wherein R 2 is CH 2 NHR 4 ; and R 4 is H, CO—(CH 2 —) n CO—R 5 , or CO—(CH 2 —) n NHR 6 .