US 7,488,818 B2
Method for producing 1,4-diphenyl azetidinone derivatives
Andreas Lindenschmidt, Bad Soden (Germany); David William Will, Kriftel (Germany); Gerhard Jaehne, Frankfurt (Germany); Theodor Andreas Wollmann, Hattersheim (Germany); Wendelin Frick, Hunstetten-Beuerbach (Germany); Bernd Junker, Bad Soden (Germany); David Rigal, Kriftel (Germany); Guenter Billen, Niedernhausen (Germany); and Heiner Jendralla, Heiner (Germany)
Assigned to Sanofi-Aventis Deutschland GmbH, Frankfurt (Germany)
Filed on Nov. 20, 2006, as Appl. No. 11/561,626.
Application 11/561626 is a continuation of application No. PCT/EP2005/005498, filed on May 20, 2005.
Claims priority of application No. 10 2004 025 071 (DE), filed on May 21, 2004; and application No. 10 2005 010 770 (DE), filed on Mar. 09, 2005.
Prior Publication US 2007/0149776 A1, Jun. 28, 2007
Int. Cl. C07D 205/08 (2006.01); C07F 9/6503 (2006.01); C07F 9/6506 (2006.01); C07F 9/6541 (2006.01); C07F 9/653 (2006.01); C07F 9/572 (2006.01); C07F 9/54 (2006.01)
U.S. Cl. 540—200  [548/208; 548/229; 548/243; 548/335.1; 548/366.4; 548/473; 548/545; 568/11] 15 Claims
 
1. A process for the preparation of 1,4-diphenylazetidinone derivatives from β-substituted amino amides which are protected, said process comprising the reaction of said amides with one or more silylating agents and at least one cyclization catalyst consisting of a salt formed by the combination of a cation and an anion, said cation represented by the general formula:

OG Complex Work Unit Drawing
wherein R16, R17, R18 and R19 are independently selected from the group consisting of aryl, (C1-C15)alkyl and benzyl,
and said anion is represented by the formula:

OG Complex Work Unit Drawing
wherein:
Z=C═O, C═S, S═O, SO2 or C═NR20
K=O, S, NR21 or CR22R23
L=NR24 or CR25R26
n=0 or 1
M=O, C═O, NR27 or CR25R29
Q=O, S, NR30, CR31R32, C═O, C═S, S═O, SO2 or C═NR34
R=CR35 or N
T=CR36 or N
U=CR37 or N
V=CR38 or N
where R20 to R32 and R34 to R38 are independently selected from the group consisting of H, (C1-C6)alkyl, aryl or heteroaryl, wherein two alkyl radicals may together also form a cycloalkylene radical with a maximum of 6 carbons in the ring which may in turn be substituted by F, Cl, Br, I, CF3, NO2, COO(C1-C6)alkyl, CON[(C1-C6)alkyl]2, cycloalkyl, (C1-C10)alkyl, (C2-C6)alkenyl, O—(C1-C6)alkyl, O—CO—(C1-C6)alkyl, O—CO—(C1-C6)alkylene-aryl, SO2N[(C1-C6)alkyl]2, S-(C1-C6)alkyl, S—(CH2-)naryl, SO—(C1-C6)alkyl, SO—(CH2-)naryl, SO2—(C1-C6)alkyl, SO2-(CH2-)naryl, SO2—N((C1-C6)alkyl)(CH2)naryl, or SO2—N((CH2-)naryl)2, where n may be 0 to 6, and the aryl radical may be substituted up to twice by F, Cl, Br, CF3, SF5, NO2, OCF3, O—(C1-C6)alkyl or (C1-C6)alkyl; or by N((C1-C6)alkyl)2, NH—CO—NH—(C1-C6)alkyl), NH—CO—NH-aryl, N[(C1-C6)alkyl]-CO—(C1-C6)alkyl, N[(C1-C6)alkyl]-COO—(C1-C6)alkyl, N[(C1-C6)alkyl]-CO-aryl, N[(C1-C6)alkyl]-COO-aryl, N[(C1-C6)alkyl]-CO—N((C1-C6)alkyl)2, N[(C1-C6)alkyl]-CO—N((C1-C6)alkyl)-aryl, N[(C1-C6)alkyl]-CO—N(aryl)2, N(aryl)-CO—(C1-C6)alkyl, N(aryl)-COO—(C1-C6)alkyl, N(aryl )-CO-aryl, N(aryl)-COO-aryl, N(aryl)-CO-N((C1-C6)alkyl)2, N(aryl)-CO—N[(C1-C6)alkyl]-aryl, N(aryl)-CO—N(aryl)2, aryl, O—(CH2-)naryl, where n may be 0 to 6, where the aryl radical may be substituted 1 to 3 times by F, Cl, Br, I, OF3, NO2, OCF3, O—(C1-C6)alkyl, (C1-C6)alkyl, N((C1-C6)alkyl)2, SF5, SO2—CH3 or COO—(C1-C6)alkyl and where R39 and R40 are independently selected from the group consisting of (C1-C6)alkyl, with the stipulation that one or more non-adjacent carbon atoms may be replaced by NH or C═O, or are (C1-C6)perfluoroalkyl, aryl or heteroaryl, or R39 and R40 together may form 1,8-naphthyl or 1,7,7-trimethylbicyclo[2.2.1]heptanyl and R40 may also be H,or where the cation component in this cyclization catalyst corresponds to the formula (XII), and the anion component is R41O−′ or where the cation component in this cyclization catalyst corresponds to formula (XII) and the anion is R42COO−, or where the cation corresponds to formula (XII), and the anion is Cl−, Br− or I−, and
R41 is aryl, (C1-C15)alkyl, benzyl,
R42 is selected from the group consisting of (C1-C15)alkyl, benzyl, (C5-C8)cycloalkyl, aryl, where aryl may be substituted by F, Cl, Br, I, —OH, —O(C1-C3)alkyl, —NH2, —NH(C1-C3)alkyl, —N[(C1-C3)alkyl]2, —C(O)OH, —C(O)O(C1-C3)alkyl, —C(O)NH2, —C(O)NH(C1-C3)alkyl, —C(O)N[(C1-C3)alkyl]2, —SO2NH2, —SO2NH(C1-C3)alkyl, —SO2N[(C1-C3)alkyl]2, —CN, (C1-C12)alkyl and (C5-C8)cycloalkyl, followed by the reaction thereof with Ag2O.