Process for producing oxazolidin-2-one derivative

Details Process for producing oxazolidin-2-one derivative Process for producing oxazolidin-2-one derivative

2000-09-08

2001-08-07

Lambkin, Deborah C. (Department: 1626)

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

Reexamination Certificate

active

06271388

ABSTRACT:

TECHNICAL FIELD
The present invention relates to a novel process for preparing an oxazolidin-2-one derivative useful for an intermediate for synthesis of medicines and agrochemicals.
BACKGRAUND ART
Oxazolidin-2-one derivatives are known from of old as industrially useful compounds. The compounds are especially useful in the medical field and many medicines prepared from the compounds have recently developed. Therefore, there are many kinds of reports on processes for preparation of the compounds. As an effective process among them is illustrated a process for preparation of the oxazolidin-2-one derivative from a 1,3-dioxolan-2-one derivative by ring-transformation.
This method is said to be an effective method, since a pre-material of a 1,3-dioxolan-2-one derivative, a starting material is prepared from a 1,2-diol derivative relatively easily available and the 1,3-oxazolidin-2-one derivative is prepared from the 1,2-diol derivative via a few steps.
Known and reported processes for preparing an oxazolidin-2-one derivative from a 1,3-dioxolan-2-one derivative by ring-transformation are illustrated as follows.
(1) The method by reacting ethylene carbonate and a N,N′-diarylurea in the presence of lithium chloride (Chem. Ber., 99, 62 (1996)). (2) The method by reacting ethylene carbonate or propylene carbonate and an arylamine in the presence of lithium chloride (Chem. Ber., 99, 55 (1996)). (3) The method by reacting 4-methoxymethyl-1,3-dioxolan-2-one and a carbamate derivative in the presence of potassium carbonate (PCT Patent Publication A No. WO97/13768). (4) The method by reacting ethylene carbonate or propylene carbonate and an isocyanate derivative in the presence of lithium chloride (Chem. Ber., 93, 1975 (1960)).
DISCLOSURE OF INVENTION
However, the above known methods have following demerits in view of the industrial application of the methods.
Namely, the methods (1) to (3) need a 1,3-dioxolan-2-one derivative in amount of 1.8 moles or more than 1.8 moles for preparing an oxazolidin-2-one derivative in some degree of the yield and therefore, are not economical. In regard to the method (4), though its yield is good, an isocyanate derivative difficult for its synthesis and handling must be used as a starting material and the method is not suitable for mass production thereof. When an optically active 1,3-dioxolan-2-one derivative as a starting material in any above method is used, the optical purity significantly decreases due to occurrence of racemization during the reaction.
The present inventors have extensively studied and have found that an oxazolidin-2-one derivative represented by the following general formula (3) is easily prepared with good yield by reacting a 1,3-dioxolan-2-one derivative represented by the following general formula (1) and a carbamate derivative or an urea derivative represented by the following general formula (2) in the presence of a fluoride salt. Furthermore, when an optically active 1,3-dioxolan-2-one derivative (1) is used in this reaction, the oxazolidin-2-one derivative (3) is also prepared in optically active form.
Namely, the present invention relates to a process for preparing an oxazolidin-2-one derivative represented by the following general formula (3)
wherein R
1
, R
2
1
R
3
and R
4
are hydrogen atom, straight, branched or cyclic alkyl group, straight or branched alkyl group substituted by alkoxy, substituted amino or alkylthio, substituted or unsubstituted aralkyl group, or substituted or unsubstituted aryl group, and R
5
is hydrogen atom, straight, branched or cyclic alkyl group, substituted or unsubstituted aralkyl group, or substituted or unsubstituted aromatic ring,
which is characterized in reacting a 1,3-dioxolan-2-one derivative represented by the following general formula (1)
wherein R
1
, R
2
, R
3
and R
4
are the same as defined above, and a carbamate derivative or an urea derivative represented by the following general formula (2)
R
5
HNCOX  (2)
wherein R
5
is the same as defined above, X is OR
6
or NR
7
R
8
in which R
6
is lower alkyl, or substituted or unsubstituted aryl, and R
7
and R
8
are independently the same as R
5
,
in the presence of a fluoride salt.
Examples of R
1
, R
2
, R
3
and R
4
in the general formula (1) are hydrogen, straight, branched or cyclic alkyl group, such as methyl, ethyl, isopropyl, cyclopropyl, or cyclohexyl, alkoxyalkyl group, such as methoxymethyl, methoxyethyl, or benzyloxymethyl, substituted aminoalkyl group, such as dimethylaminomethyl, piperidinoethyl, morpholinoethyl, N-benzyloxycarbonylpiperadinomethyl, N-methylpiperazinomethyl, or N-ethoxycarbonylmethyl-piperazinomethyl, alkylthioalkyl group, such as methylthiomethyl, or methylthioethyl, substituted or unsubstituted aralkyl group, such as benzyl, methylbenzyl, or methoxybenzyl, and substituted or unsubstituted aryl group, such as phenyl, tolyl, or methoxyphenyl. Preferable groups among them are hydrogen, C
1
-C
4
lower alkyl group, methoxymethyl, benzyloxymethyl and benzyl.
Examples of R
5
in the general formula (2) are hydrogen, straight, branched or cyclic alkyl group, such as methyl, ethyl, isopropyl, or cyclopropyl, substituted or unsubstituted aralkyl group, such as benzyl, methybenzyl, or methoxybenzyl, substituted or unsubstituted aryl group, such as phenyl, cyanophenyl, tolyl, or methoxyphenyl, aromatic polycyclic ring, such as naphthalene or anthracene, or aromatic heterocyclic ring, such as furyl, thienyl, pyridyl, pyrimidinyl, quinolyl, benzofuryl, or benzothienyl. Preferable groups among them are hydrogen, C
1
-C
4
lower alkyl group, benzyl, phenyl, cyanophenyl, naphthyl, or thienyl.
Examples of R
6
in the general formula (2) are lower alkyl group, such as methyl, ethyl, or t-butyl, or substituted or unsubstituted aryl group, such as phenyl, methoxyphenyl, or nitrophenyl. Examples of R
6
or R
7
are the same as examples of R
5
. Preferable examples of them are C
1
-C
4
lower alkyl and phenyl.
The amount of the carbamate derivative or the urea derivative (2) is 0.5 mole or more than 0.5 mole to 1,3-dioxolan-2-one derivative (1), preferably 0.8 to 1.5 moles, further preferably 0.9 to 1.1 moles.
The fluoride salts are preferably quaternary ammonium fluorides, alkali metal fluorides, or alkaline earth metal fluorides, especially preferably alkali metal fluorides or alkaline earth metal fluorides. These salts may be used alone or in combination of them and may be used in form being supported on an appropriate carrier.
Examples of the quaternary ammonium fluorides are tetramethylammonium fluoride, tetraethylammonium fluoride, tetrabutylammonium fluoride, tetraoctylammonium fluoride, and benzyltrimethylammonium fluoride.
Examples of the alkali metal fluorides are sodium fluoride, potassium fluoride, and cesium fluoride. Examples of the alkaline earth metal fluorides are magnesium fluoride and calcium fluoride. Examples of the carrier are zeolite, alumina, silica gel, molecular sieves, modified material thereof and so on.
The amount of the fluoride salt is preferably 0.001 to 10 moles to the substrate, a 1,3-dioxolan-2-one derivative, especially preferably 0.01 to 1 mole. To use it less than 0.001 mole makes the reaction very slow. On the other hand, to use it in excess of 10 moles does not give bad effect the reaction, but it is not economical. Depending on the solvent, the excess of the salt becomes insoluble and to stir the reaction mixture becomes difficult.
The solvents are aprotic solvents, such as N,N-dimethylformamide or dimethyl sulfoxide, ethers, such as diglyme, triglyme, 1,4-dioxane, 1,2-dimethoxyethane, or t-butylmethyl ether, chlorinated solvents such as chloroform or dichloroethane, or a mixture thereof, preferably N,N-dimethylformamide or dimethyl sulfoxide.
The reaction temperature is from 50° C. under heating to reflux temperature of the solvent, preferably from 100° C. to 150° C.
After finishing the reaction, insoluble materials such as a metal fluoride are removed by filtration, excess solvent is distilled off in vacuo, and the residue is purified by distillation, recrys

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