Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2002-03-18
2004-03-02
McKane, Joseph K. (Department: 1626)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
C548S232000
Reexamination Certificate
active
06699995
ABSTRACT:
TECHNICAL FIELD
The present invention relates to an industrially advantageous production method for forming a carbon-carbon bond at the 5-position of oxazole.
BACKGROUND ART
There are various production methods (e.g. WO97/36882) of compounds having a carbon substituent (a group bonded via a carbon) bonded at the 5-position of oxazole. Most of them require introduction of a necessary carbon substituent before constructing an oxazole ring. However, the starting material usable for the production method is limited and the synthesis thereof is associated with difficulty.
In view of the above, the development of an easy and simple method for introducing a carbon substituent into the 5-position of oxazole is highly significant, and finding of a reaction permitting direct formation of a carbon-carbon bond on an oxazole having no substituent at the 5-position is extremely significant.
DISCLOSURE OF INVENTION
The present inventors have conducted intensive studies in an attempt to introduce a carbon substituent into the 5-position of oxazole and found for the first time that a reaction of an oxazole having no substituent at the 5-position (particularly one having an oxo group or amino group at the 2-position) with olefin in the presence of an acid or base unexpectedly results in an easy reaction with the olefin and the formation of a carbon-carbon bond at the 5-position of the oxazole, based on which they investigated further and completed the present invention.
Accordingly, the present invention relates to:
(1) a method of producing a compound represented by the formula
wherein
R
1
and R
2
are each a hydrogen atom, an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group,
R
3
is an electron-withdrawing group, and
R
4
, R
5
and R
6
are each a hydrogen atom or an optionally substituted hydrocarbon group, or a salt thereof, which method comprises reacting a compound represented by the formula
wherein the symbols in the formula are as defined above, or a salt thereof, with a compound represented by the formula
wherein the symbols in the formula are as defined above, or a salt thereof, in the presence of an acid or a base;
(2) the production method of the aforementioned (1), wherein R
1
and R
2
are each a hydrogen atom, an optionally substituted alkyl group, an optionally substituted aralkyl group, an optionally substituted aryl group or an optionally substituted heterocyclic group;
(3) the production method of the aforementioned (1), wherein R
1
is an optionally substituted aryl group or an optionally substituted aromatic heterocyclic group;
(4) the production method of the aforementioned (1), wherein R
1
is an optionally substituted phenyl group;
(5) the production method of the aforementioned (1), wherein R
2
is a hydrogen atom;
(6) the production method of the aforementioned (1), wherein R
4
, R
5
and R
6
are each a hydrogen atom, an optionally substituted alkyl group or an optionally substituted aryl group;
(7) the production method of the aforementioned (1), wherein R
4
, R
5
and R
6
are each a hydrogen atom;
(8) the production method of the aforementioned (1), wherein R
3
is —CN, —COOR
7
(R
7
is a hydrogen atom or an optionally substituted hydrocarbon group) or —COR
8
(R
8
is a hydrogen atom, an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group);
(9) the production method of the aforementioned (1), wherein R
3
is —CN;
(10) the production method of the aforementioned (1), wherein R
3
is —COOR
7
(R
7
is a hydrogen atom or an optionally substituted alkyl group);
(11) the production method of the aforementioned (1), wherein R
3
is —COR
8
(R
8
is a hydrogen atom, an optionally substituted alkyl group or an optionally substituted aryl group);
(12) the production method of the aforementioned (1), wherein the reaction is carried out in the presence of an acid;
(13) a method of producing a compound represented by the formula
wherein
R
1
is a hydrogen atom, an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group,
R
18
is an optionally substituted amino group, and other symbols are as defined above, or a salt thereof, which method comprises reacting a compound represented by the formula
wherein the symbols in the formula are as defined above, or a salt thereof, with a compound represented by the formula (II) or a salt thereof, in the presence of an acid;
(14) a method of producing a compound represented by the formula
wherein
R
1
is as defined above,
R
4
, R
5
, R
6
are each a hydrogen atom or an optionally substituted hydrocarbon group,
R
19
is an optionally substituted heterocyclic group containing nitrogen, which is bonded via a nitrogen atom, and
R
20
is an optionally substituted hydrocarbon group, or a salt thereof, which method comprises reacting a compound represented by the formula (I) or a salt thereof with a compound represented by the formula
wherein R
7
is a hydrogen atom or an optionally substituted hydrocarbon group, and other symbols are as defined above, or a salt thereof, in the presence of an acid or a base to give a compound represented by the formula
wherein the symbols in the formula are as defined above, or a salt thereof, subjecting this compound to halogenation reaction to give a compound represented by the formula
wherein X is a halogen atom, and other symbols are as defined above, or a salt thereof, reacting this compound with a compound represented by the formula: R
19
—H (XII) [R
19
is as defined above] to give a compound represented by the formula
wherein the symbols in the formula are as defined above, or a salt thereof, subjecting this compound to a reduction reaction to give a compound represented by the formula
wherein the symbols in the formula are as defined above, or a salt thereof, reacting this compound with a compound represented by the formula: R
10
SO
2
Cl (XV) [R
10
is an optionally substituted alkyl group or an optionally substituted aryl group] or a halogenating agent to give a compound represented by the formula
wherein Za is a halogen atom or —OSO
2
R
10
(R
10
is as defined above), and other symbols are as defined above, or a salt thereof, and reacting this compound with a compound represented by the formula: R
20
—OH (XVII) [R
20
is as defined above];
(15) a method of producing a compound represented by the formula (XVIII) or a salt thereof, which comprises reacting a compound represented by the formula (IX) or a salt thereof with a compound represented by the formula (IIa) or a salt thereof in the presence of an acid to give a compound represented by the formula
wherein the symbols in the formula are as defined above, or a salt thereof, subjecting this compound to halogenation reaction to give a compound represented by the formula (XIa) or a salt thereof, reacting this compound with a compound represented by the formula (XII) to give a compound represented by the formula (XIII) or a salt thereof, subjecting this compound to a reduction reaction to give a compound represented by the formula (XIV) or a salt thereof, reacting this compound with a compound represented by the formula (XV) or halogenating agent to give a compound represented by the formula (XVI) or a salt thereof, and reacting this compound with a compound represented by the formula (XVII);
(16) methyl. 4-(4-chlorophenyl)-2-(2-methylimidazol-1-yl)-5-oxazolepropionate; and the like.
The “hydrocarbon group” of the above-mentioned “optionally substituted hydrocarbon group” represented by R
1
, R
2
, R
4
, R
5
, R
6
, R
7
or R
8
is exemplified by aliphatic hydrocarbon group, alicyclic hydrocarbon group, aryl group, aralkyl group and the like.
Examples of the aliphatic hydrocarbon group include linear or branched aliphatic hydrocarbon group having 1 to 15 carbon atom(s), such as alkyl group, alkenyl group, alkynyl group and the like, with preference given to alkyl group.
Preferable examples of alkyl group include alkyl group
Ikeuchi Motoki
Ohashi Norihiko
Tawada Hiroyuki
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