Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2002-02-08
2004-09-21
McKane, Joseph K. (Department: 1626)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
C548S556000, C558S044000
Reexamination Certificate
active
06794519
ABSTRACT:
TECHNICAL FIELD
The present invention relates to a method of producing sulfonic acid ester derivatives, which are useful as intermediates for the synthesis of fine chemicals such as medicinal compounds and agrochemicals, represented by the general formula (4):
or the general formula (5):
wherein n represents an integer of 0 to 5, A represents a phenyl group, which may be substituted, B and B′ may be the same or different and each represents a phenyl group, which may be substituted, a straight or branched alkyl group containing 1 to 4 carbon atoms or a hydrogen atom, D represents a straight or branched alkyl group containing 1 to 8 carbon atoms, which may be substituted, or a hydrogen atom, E represents a straight or branched alkylene group containing 1 to 8 carbon atoms, which may be substituted, F represents a straight or branched alkyl group containing 1 to 8 carbon atoms, which may be substituted, and R represents a methanesulfonyl, ethanesulfonyl, p-toluenesulfonyl or p-nitrobenzenesulfonyl group.
BACKGROUND ART
Known in the art for producing sulfonic acid ester derivatives represented by the above general formula (4) or (5) are the method comprising reacting the corresponding amino alcohol derivative with an organic sulfonyl halide in an organic solvent in the presence of an organic base, for example a tertiary amine such as triethylamine or an aromatic amine such as pyridine, or in such an organic base; and the method comprising reacting the corresponding amino alcohol derivative with an organic sulfonyl halide in an anhydrous organic solvent in the presence of a water-prohibiting base such as sodium hydride or sodium amide.
Specifically, there are known the method comprising reacting 1-benzyl-3-pyrrolidinol with methanesulfonyl chloride or toluenesulfonyl chloride in the presence of an organic base such as triethylamine or pyridine (JP-A-07-116138; J. Med. Chem., 35 (1992) 22, 4205-4213) and the method comprising reacting 1-benzyl-3-pyrrolidinol with toluenesulfonyl chloride in an anhydrous solvent such as benzene or tetrahydrofuran in the presence of a water-prohibiting base such as sodium hydride or sodium amide (JP-A-51-125286; Laid-open European Pantent EP-0928787), among others.
However, these known production methods have the following problems, among others:
1) When an organic base such as a tertiary amine or an aromatic amine is used, the organic base is expensive. For isolating the sulfonic acid ester formed as an intermediate for the synthesis of fine chemicals such as medicinal compounds or agrochemicals, which are required to be of high quality, a high-level of purification for removal of the organic base, such as crystallization, distillation and/or column chromatography, is required (since the product sulfonic acid ester derivative itself is a kind of organic base, it is difficult to purify the same by such a simple technique as phase separation). The organic base is obtained as waste in an amount at least one equivalent relative to the product sulfonic acid ester derivatives.
2) When a water-prohibiting base, such as sodium hydride or sodium amide, is used, such water-prohibiting base itself is expensive. Such water-prohibiting base has a safe problem in handling in using it on a commercial scale.
3) In all the known methods, a high-level of purification, for example removal of the organic base by rectification, and/or dehydration, is required if the solvent is to be recovered and recycled. Such a purification process is economically difficult in many cases and the solvent is discharged as waste in increased amounts.
Thus, when evaluated as methods capable of reducing the load on the environment in the production of intermediates for high-quality fine chemicals such as medicinal compounds and agrochemicals on a commercial scale and in an economical manner, the prior art methods have problems.
In view of the state of the art as mentioned above, it is an object of the present invention to provide a method of economically producing the sulfonic acid ester derivatives represented by the general formula (4) or (5), which are intermediates for the synthesis of fine chemicals such as medicinal compounds or agrochemicals, which are required to be of high quality, in a simple and easy and safe manner while reducing the load on the environment.
DISCLOSURE OF INVENTION
The present invention thus provides a method of producing a sulfonic acid ester derivative represented by the general formula (4):
or the general formula (5):
wherein n represents an integer of 0 to 5, A represents a phenyl group, which may be substituted, B and B′ are the same or different and each represents a phenyl group, which may be substituted, a straight or branched alkyl group containing 1 to 4 carbon atoms or a hydrogen atom, D represents a straight or branched alkyl group containing 1 to 8 carbon atoms, which may be substituted, or a hydrogen atom, E represents a straight or branched alkylene group containing 1 to 8 carbon atoms, which may be substituted, F represents a straight or branched alkyl group containing 1 to 8 carbon atoms, which may be substituted and R represents a methanesulfonyl, ethanesulfonyl, p-toluenesulfonyl or p-nitrobenzenesulfonyl group, which comprises reacting an amino alcohol derivative represented by the general formula (1):
or the general formula (2):
wherein n, A, B, B′, D, E and F are as defined above, with an organic sulfonyl halide represented by the general formula (3):
R—X
wherein R is as defined above and X represents a chlorine, bromine or iodine atom,
in a mixed solvent composed of an aprotic organic solvent and water in the presence of a non-water-prohibiting inorganic base.
In the following, the present invention is described in detail.
The amino alcohol derivative represented by the general formula (1):
or the general formula (2):
and to be used in the production method of the present invention can be produced, for example, by the method described in JP-A-61-63652 or in JP-A-01-141600.
Referring to the above general formula (1), n represents an integer of 0 to 5 and preferably is an integer of 0 to 4, more preferably an integer of 2 or 3.
The substituent A in the above general formula (1) or (2) is a phenyl group, which may be substituted, and specifically includes an unsubstituted phenyl group, a nitro-substituted phenyl group, a halo-substituted phenyl group, a phenyl group substituted by one or two lower alkoxyl groups or one or two lower alkyl groups, and the like.
The substituents B and B′ in the above general formula (1) or (2) may be the same or different and each represents a phenyl group, which may be substituted, a straight or branched alkyl group containing 1 to 4 carbon atoms, or a hydrogen atom. Specifically, there may be mentioned hydrogen; lower alkyl groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl and tert-butyl; unsubstituted phenyl, nitro-substituted phenyl, phenyl substituted by one or two lower alkoxyl groups, and the like.
The substituent D in the above general formula (1) represents a straight or branched alkyl group containing 1 to 8 carbon atoms, which may be substituted, or a hydrogen atom. This alkyl group may be unsubstituted or substituted by a substituent inert to the sulfonylation reaction, for example a protected amino group such as a tertiary amino or acylamino group; a substituted carbonyl group such as a hydoxycarbonyl, alkoxycarbonyl, aminocarbonyl or acyl group; a protected hydroxyl group such as an alkyloxy or acyloxy group; an aromatic group such as a phenyl or pyridyl group; or the like.
The substituent E in the above general formula (1) represents a straight or branched alkylene group containing 1 to 8 carbon atoms, which may be substituted, and the substituent F represents a straight or branched alkyl group containing 1 to 8 carbon atoms, which may be substituted. The alkylene group and alkyl group may be unsubstituted or substituted by such a substituent inert to the sulfonylation reaction as described above.
As specific examples of the amino alco
Kano Fumihiko
Kunihiro Shigeki
Mori Natsuki
Yoshida Noritaka
Kaneka Corporation
McKane Joseph K.
Shameem Golam M M
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