Jun.22,2006  13  US 2006/0135784 Al  tion, under reaction conditions of the above third step  followed:  [0143]  Thus, if a mixture of erythro-isomer (3) and threo› isomer (3) is used, it is possible to convert erythro-isomer  (3) selectively into threo-isomer ( 4) having an inverted steric  configuration at 2-position carbon, and at the same time, to  retain threo-isomer (3) as it is, in the second step, as shown  in the above scheme. Subsequently, in the third step, leaving  group L ofretained threo-isomer (3) may be converted into  a hydroxyl group to obtain threo-isomer ( 4), and then,  substituents may he removed to obtain 3-amino-2-hydrox› ypropionic acid derivative (1) having a threo configuration  [hereinafter, also referred to as threo-isomer (1)]. This  process can greatly increase the diastereomer excess of the  products.  [0144]  In the above process, R$^{1 }$is a substituted or unsub› stituted alkyl group having 1 to 30 carbon atoms, a substi› tuted or unsubstituted aryl group having 6 to 30 carbon  atoms, or a substituted or unsubstituted aralkyl group having  7 to 30 carbon atoms, and R $^{2 }$is a hydrogen atom. However,  R$^{1 }$is preferably a substituted or unsubstituted aralkyl group  having 7 to 30 carbon atoms, more preferably a substituted  or unsubstituted benzyl group, and most preferably an  unsubstituted benzyl group. Also, leaving group L is pref› erably the above sulfonyloxy group.  [0145]  In the above process, in order to convert erythro› isomer (3) into three-isomer ( 4) having an inverted steric  configuration at 2-position carbon, and at the same time, to  retain threo-isomer (3) as it is, it is preferable to carry out the  reaction in the above second step under mild conditions, for  example, by using an acidic substance or a basic substance  in a small amount, by retaining a low reaction temperature  or by combining these conditions. As the conditions become  mild, it is possible to retain threo-isomer (3) efficiently.  [0146]  The above acidic substance is not limited to a  particular one and may be selected from acidic substances  used in the above second step. The amount of the acidic  substances used varies depending on the kind of acids, and  they are usually used in a molar amount below 5-fold,  preferably in a molar amount below 2-fold, and more  preferably in a molar amount below I-fold, relative to the  total amount of erythro-isomer (3) and threo-isomer (3).  [0147]  The above basic substance is not limited to a  particular one and weakly basic substances used in the above  second step are preferably used. Among others, N,N-dim› ethyl formamide, pyridine or the like may be used prefer› ably. The amount of the above basic substances used varies  depending on the kind of bases, and they are usually used in  a molar amount below 50-fold, preferably in a molar amount  below 20-fold, and more preferably in a molar amount  below 10-fold, relative to the total amount of erythro-isomer  (3) and threo-isomer (3).  [0148]  Also, the reaction temperature varies, for example,  depending on the kind of the above acidic substances or  basic substances, the amount of them used and the like, and  it may be usually below 120°  C., preferably below 100°  C.,  and more preferably below 80°  C.  [0149]  Reaction solvents used in this reaction are not  limited to particular ones and, various organic solvents used  in the above second step may be used. Examples of the  reaction solvents include, for example, aliphatic hydrocar› bons such as hexane, heptane or methylcyclohexane; aro› matic hydrocarbons such as toluene or xylene; halogenated  hydrocarbons such as methylene chloride or chloroform;  ethers such as tetrahydrofuran, 1,4-dioxane or t-butyl methyl  ether; aliphatic acid esters such as methyl acetate, ethyl  acetate or isopropyl acetate; nitriles such as acetonitrile;  alcohols such as methanol, ethanol, isopropanol or benzyl  alcohol. Toluene is a particularly preferable aromatic hydro› carbon, 1,4-dioxane is a particularly preferable ether, and  ethyl acetate is a particularly preferable aliphatic acid ester.  Among others, aromatic hydrocarbons are preferably used.  These organic solvents may be used alone or in a mixture of  two or more solvents. Besides, if the basic substances used  in the above second step are liquid at the above reaction  temperature, the above basic substances may be used so as  to also serve as a reaction solvent.  [0150]  By the above process, it is possible to obtain  3-amino-2-hydroxy-4-phenylbutyric acid wherein the dias› tereomer excess of the threo-isomer is 87% d.e. from  N-ethoxycarbony 1-3-amino-2-methanesulfony loxy-4-phe› nylbutyric acid methyl ester [in the above general formula  (2), R$^{1}$=benzyl group, R$^{2}$=hydrogen atom, P$^{1}$=ethoxycarbo› nyl group, and R $^{4}$=methyl group] wherein the diastereomer  excess of the erythro-isomer is 66% d.e., for example, as  shown in Example 9 below. Thus, the process can greatly  increase the diastereomer excess.  [0151]  As described above, according to the present  invention, itis possibleto prepare conveniently and efficiently,  and with industrial advantages, 3-amino-2-hydroxypropi› onic acid derivatives (1) having a particular steric configu› ration from N-protected-3-amino-2-hydroxypropionic acid  derivatives (2) having a reverse steric configuration at  2-position carbon.  H  R3  H  R3  I  I  R $^{1}$-C-N-S1  I  I  R $^{1}$-C-N-S6  I  I  L-C-H  H-c-o-s 5  I  coos 3  I  coos 4  erythro (3)  2nd step  threo (4)  3rd step  +  H  R3  H  R3  I  I  R $^{1}$-C-N-S1  I  I  R $^{1}$-C-N-S1  I  I  H-C-L  H-C-L  I  coos 3  I  coos 10  threo (3)  threo (3)  H  R 3  I  I  R I  H-C-OH  I  COOR  threo (1)  [0141]  wherein R 1 , R 2 , R 3 , S1, S 3 , S 4 , S 5 , S 6  and Lare  as defined above; and  [0142]  S $^{10 }$represents a hydrogen atom or an ester resi- due. 