Processes for preparing of glucopyranosyl-substituted benzyl-benzene derivates and intermediates therein
The present invention relates to processes for preparing the compounds of general formula I, wherein the groups R 1 and R 3 are defined according to claim 1 . Furthermore this inventions relates to intermediates obtained in these processes.
1. Process for preparing the compounds of general formula V,
wherein
R 1 denotes R tetrahydrofuran-3-yl or S-tetrahydrofuran-3-yl; and
X denotes a bromine atom or a iodine atom;
said method comprised of the steps of reacting a benzoyl chloride derivative of the formula XII
wherein X is defined as above; or a derivative thereof such as a benzoyl anhydride, an ester or a benzonitrile;
with a halobenzene of the formula XXVII
wherein Z 5 denotes a fluorine, chlorine or iodine atom;
in the presence of a catalyst to obtain an intermediate compound of the formula XXVI
wherein X and Z 5 are defined as hereinbefore; and
reacting the intermediate compound of the formula XXVI with R 1 —OH, wherein R 1 is defined as hereinbefore, or an anion thereof, in the presence of a base to yield a benzophenone derivative of the formula VII
wherein X and R 1 are defined as hereinbefore; and
the benzophenone derivative of the formula VII is reacted with a reducing agent in the presence of a Lewis acid to furnish the compound of the formula V as defined above.
2. Compound of general formula VI
wherein
R 1 denotes R tetrahydrofuran-3-yl or S-tetrahydrofuran 3 yl; and
M denotes Li or MgHal, wherein Hal denotes Cl, Br or I.
3. Compound selected from the group consisting of:
(S)-4-bromo-1-chloro-2-(4-tetrahydrofuran-3-yloxy-benzyl)-benzene;
(R)-4-bromo-1-chloro-2-(4-tetrahydrofuran-3-yloxy-benzyl)-benzene;
(S)-4-iodo-1-chloro-2-(4-tetrahydrofuran-3-yloxy-benzyl)-benzene; or
(R)-4-iodo-1-chloro-2-(4-tetrahydrofuran-3-yloxy-benzyl)-benzene.
4. Compound of general formula VII
or of the formula XIX
wherein
R 1 denotes R tetrahydrofuran-3-yl or S-tetrahydrofuran 3 yl; and
X denotes Br or I.
5. Compound of the formula VII according to claim 4 selected from the group consisting of
(5-bromo-2-chloro-phenyl)-(4-(R)-tetrahydrofuran-3-yloxy-phenyl)-methanone;
(5-bromo-2-chloro-phenyl)-(4-(S)-tetrahydrofuran-3-yloxy-phenyl)-methanone;
(5-iodo-2-chloro-phenyl)-(4-(R)-tetrahydrofuran-3-yloxy-phenyl)-methanone;
(5-iodo-2-chloro-phenyl)-(4-(S)-tetrahydrofuran-3-yloxy-phenyl)-methanone.
6. Compound selected from the group consisting of
(5-bromo-2-chloro-phenyl)-(4-fluoro-phenyl)-methanone;
(5-iodo-2-chloro-phenyl)-(4-fluoro-phenyl)-methanone.