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Method for Preparing Higly Optically Active 2-Sufonyloxy-1-Phenylethanol Derivatives
Korea Health Industry Development Institute (KHIDI) South Korea flag South Korea
Abstract ID:
More effective methods for preparing 2-sufonyloxy-1-phenylethanol derivatives in a high yield and a high e.e. value are now required in the industries of pharmacy...
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MECHANISM OF ACTION
Efficient Method for Preparing Optically Active 2-Sulfonyloxy-1-Phenylethanol derivatives, High e.e.(enantiomeric exess) Value of Product, Strong IP Position, Safe Process.

The core technology of Dr. Kee-In, Lee and Dr. Do-Min, Lee  is to provide novel method for preparing higly optically active 2-sulfonyloxy-1-phenylethanol derivatives of formula 1 by using a rhodium compoud catalyst.  Rhodium compound of formula 2 or 3 reduce α-sulfonyloxy acetophenone compound asymetrically in a high e.e. value.                                                  


Background and unmet needs: Opticlly active 2-sulfonyloxy-1-phenylethanol derivatives of formula 1 are essential intermediate for producing 2-amino-1-phenylethanol derivatives which have been used in the preparations of several agricultural chemicals, medical supplies, fine chemicals and building blocks, and 60 biologically active substances. The asymmetric reduction of α-substituted acetophenone using oxazaborolidine catalyst and borane is mainly employed method in the preparation of 2-sulfonyloxy-1-phenylethanol derivatives. However, such method require high cost due to the use of expensive catalyst in an excess amount, and have wide fluctuation of the optical activity of the product depending on the substitution of the phenyl moiety, in addition, the reduction is highly sensitive to humidity.


Overall Reaction Scheme of Preparing 2-sulfonyloxy-1-phenylethanol derivatives : Generally, the compound of formula1 is prepared by conventional method using acetophenon as starting material and α-mesyloxy acetophenone as essential intermediate.  


Wherein, X is a halogen atom such as -Cl and –Br, or a leaving group such as mesyloxy (-OMs) and tosyloxy (-OTs) ; R is one or more substituents, each independently, selected from the group of H, F, Cl, Br, OMe, OBn, NO2, CF3, Me, tert-Bu, CH2OMe (Me=methyl, Bn=benzyl, Bu= Butyl).


The α-sulfonyloxy acetophenone compound used in the above process may be prepared by a conventional method ; for instance, the α-tosyloxy acetophenone compound may be prepared by reacting acetophenone with [hydroxyl(tosyloxy)iodido] benzene and similary, the α-mesyloxy acetophenone compound may be prepared by reacting acetophenone with [hydroxyl(mesyloxy)iodido] benzene.


Rhodium compound of formula 2 or 3 reduce α-acetophenone compound asymetrically to produce optically active 2-sulfonyloxy-1-phenylethanol derivatives.


Preparation of the rhodium catalyst of formula 2 and 3


The rhodium catalyst can be obtained in a yield of 70% by reacting 1 equivalent of (pentamethylcyclopentadienyl) rhodium(III) chloride dimer ([Rh(C5Me5)Cl2J2), 2 equivalent of optically active l,2-diphenylethylene-N-(p-toluenesulfonyl)diamine (TsDPEN) and 4 equivalent of triethylamine in methylene chloride, and washing and recrystallizing the reaction mixture. Not only by the conventional methods above, the rhodium catalyst of formula 2 and 3 may be prepared by methods (A) and (B) described below.


Method (A) - reacting 1 equivalent of (pentamethylcyclopentadienyl)rhodium(lll) chloride dimer, 2 equivalent of optically active 1,2-diphenylethylene-N-(p-toluenesulfonyl)diamine(TsDPEN) and 4 equivalent of triethylamine in methylene chloide as a solvent to obtain a reaction mixture, and removing the solvent from the reaction mixture ; and


Method (B) – reacting 1 equivalent of (pentamethylcyclopentadienyl)rhodium(lll) chloride dimer and 2 equivalent of optically active 1,2-diphenylethylene-N-(p-toluenesulfonyl)diamine(TsDPEN) in methylene chloide as a solvent, in the absence of triethylamine, to obtain a reaction mixture, and removing the solvent from the reaction mixture.


The compound of formula 2 and 3 can be easily and efficiently prepared by the method (A) and (B) in a higher yield than that of conventional method, and therefore, the compound of formula 1 obtained in the asymmetrical reduction of α- chloro acetophenones using the catalyst of formula 2 or 3 exhibits a higher e.e. value than that of the products obtained in the conventional methods.

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Development collaboration, or non-exclusive or exclusive licensing agreement.
FEATURED
Last Updated Jun 2016
Technology Type MECHANISM
Phase of Development EARLY STAGE
GOVERNMENT INSTITUTE