Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1992-08-21
1993-10-26
Evans, Joseph E.
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
549549, C07D30132, C07D30312
Patent
active
052568032
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to a new process for the preparation of (2R,3R)-.beta.-phenylglycidic acid of formula: ##STR1## optionally in salt or ester form.
BACKGROUND OF THE INVENTION
Products of general formula (I) can be employed to prepare taxol under the conditions described in papers by J-N. Denis et al., J. Org. Chem., 51, 46-50 (1986); J. Amer. Chem. Soc., 110, 5917-5919 (1988) or the taxol derivatives which are described in European Patent EP 253,738.
It is known, in particular according to J-N. Denis et al., J. Org. Chem., 51, 46-50 (1986), to prepare the products of general formula (I) by titanium-catalyzed asymmetric epoxidation (T. Katsuki and K. B. Sharpless, J. Amer. Chem. Soc., 102, 5974-5976 (1980); J. G. Hill et al., J. Org. Chem., 48, 3607 (1983)) of cis-cinnamic alcohol, followed by oxidation and esterification of the epoxyalcohol obtained. However, the yields are not satisfactory, the enantiomer excesses are generally lower than 80% and the route is relatively long.
According to K. Harada, J. Org. Chem., 31, 1407-1410 (1966), it is known to separate the isomers of trans-.beta.-phenylglycidic acid by precipitation of a salt with optically active .alpha.-methylbenzylamine.
According to K. Harada and Y. Nakajima, Bull. Chem. Soc. Japan, 47 (11) 2911-2912 (1974), it is known to separate the isomers of cis-.beta.-phenylglycidic acid by precipitation of a salt with optically active ephedrine.
Application EP 0,342,903 describes the separation of an enantiomer of .beta.-(4-methoxyphenyl)glycidic acid from the corresponding diastereomer by means of optically active .alpha.-methylbenzylamine.
However, to make it possible for these processes to be carried out, the cis and trans isomers of .beta.-phenylglycidic acid must be separated beforehand.
It has now been found, and it is this that forms the subject of the present invention, that (2R,3R)-.beta.-phenylglycidic acid can be obtained from a mixture of the cis and trans isomers.
DESCRIPTION OF THE INVENTION
The process according to the invention consists in crystallizing in a suitable solvent the salt of (2R,3R)-.beta.-phenylglycidic acid with the (R)(+)-.alpha.-methylbenzylamine present in a mixture of (R)(+)-.alpha.-methylbenzylamine salts with (2R,3R)-.beta.-phenylglycidic acid, (2S,3S)-.beta.-phenylglycidic acid, (2R,3S)-.beta.-phenylglycidic acid and (2S,3R)-.beta.-phenylglycidic acid.
Solvents which may be employed are water or an organic solvent chosen from aliphatic alcohols containing 1 to 4 carbon atoms, such as methanol or ethanol, ethers or ketones, optionally mixed with water.
The precipitation of the salt of (2R,3R)-.beta.-phenylglycidic acid with (R)(+)-.alpha.-methylbenzylamine is generally performed by adding acetone to an aqueous or organic, preferably ethanolic, solution of the mixture of the salts of the optical isomers of cis and trans .beta.-phenylglycidic acids with (+)-.alpha.-methylbenzylamine.
When the operation is performed in organic medium, it is particularly advantageous to add the acetone to the organic solution at reflux and then to make the desired salt precipitate on cooling.
When the operation is performed in aqueous medium, it is particularly advantageous to add the acetone until a mixture containing from 25 to 50% of water and from 75 to 50% of acetone is obtained. The best results are preferably obtained when the crystallization solution contains approximately 35% of water and 65% of acetone.
The mixture of the salts of the optical isomers of cis and trans .beta.-phenylglycidic acids with (R)(+)-.alpha.-methylbenzylamine can be obtained: and trans isomers of .beta.-phenylglycidic acid which is prepared in situ, or hydrochloride, on the mixture of the alkali metal salts, such as the potassium salts, of cis and trans .beta.-phenylglycidic acids.
The mixture of the alkali metal salts of cis and trans .beta.-phenylglycidic acids can be obtained by saponifying the corresponding esters with an inorganic base. It is particularly advantageous to employ ethanolic potassium hydroxide, t
REFERENCES:
patent: 3901915 (1975-08-01), Perry et al.
Duchesne Jean-Pierre
Mulhauser Michel
Evans Joseph E.
Rhone-Poulenc Rorer S.A.
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