Jun.22,2006  6  US 2006/0135784 Al  (4a), or by substitution of an alkoxy group (-OR 4 )  of an  alkoxycarbonyl group (-COOR 4 )  of the above N-alkoxy› carbonyl-3-amino-2-hydroxypropionic acid derivative ( 4b)  with a 2-position hydroxyl group in the same molecule. In  this connection, the oxazolidinone derivative ( 4c) can be  formed whether water coexists in this step or not.  [0063]  In  the  substituted-3-amino-2-hydroxypropionic  acid derivatives (4) obtained in this step, S 4  (or S 7 , S $^{8 }$or S9 )  represents a hydrogen atom or an ester residue. The above  ester residue represents a monovalent organic group which  can serve as an ester-type protecting group for a carboxyl  group, for example, by being included in a structure repre› sented by ----COOS 4  or the like. The above monovalent  organic group is not limited to a particular one if it has an  effect of protecting the carboxyl group, and may be selecter  from the ester-type protecting groups as described, for  example, in PROTECTIVE GROUPS IN ORGANIC SYN› THESIS, 2nd ed., JOHN WILLY & SONS pub!. (1991).  Among others, a lower alkyl group having 1 to 4 carbon  atoms or a substituted or unsubstituted benzyl group is  preferably used. A lower alkyl group having 1 to 4 carbon  atoms is more preferably used and a methyl group or an  ethyl group is further preferably used. A methyl group is  most preferably used.  [0064]  S 3  in the N-protected-3-aminopropionic  acid  derivatives (3) and S 4  (or S 7 , S 8  or S 9 ) in the substituted-3- amino-2-hydroxypropionic acid derivatives (4) may be the  same.  [0065]  It  is simple and convenient if they are the same, and  generally, they are often the same. However, they may be  converted by esterification, hydrolysis, transesterification or  the like under the conditions of this reaction. Furthermore,  it necessary, known esterification, hydrolysis, transesterifi› cation or the like may be introduced into this step, and they  may be freely selected in a range of not affecting the step.  For example, if S 3  is an ester residue in the 3-aminopropi› onic acid derivatives (3), for example, this reaction may be  preferably carried out in the presence of water ( or using  water as a reaction solvent), and if necessary, the ester site  may be hydrolyzed, to derive substituted-3-amino-2-hy› droxypropionic acid derivatives ( 4) wherein S $^{4 }$is a hydrogen  atom.  [0066]  Next, reaction conditions of the second step are  described.  [0067]  Preferably, this reaction is carried out under heat› ing. The reaction temperature is not limited to a particular  range if it is below the boiling point of the reaction mixture.  It  may be preferably above 40°  C., more preferably above  60°  C., and most preferably above 80°  C. In general, as the  temperature becomes higher, the reaction proceeds more  rapidly.  [0068]  Also, in this step, an acid treatment or abase  treatment may be carried out for the purpose of promoting  the reaction, if necessary, by coexistence or addition of a  suitable amount of an acidic substance or a basic substance  as a reaction accelerator. This treatment allows the reaction  to proceed repidly at a lower temperature, and therefore, it  is possible to carry out the inversion step at a milder treating  temperature or a far milder treating temperature. The treat› ing temperature in this case is usually below about 40°  C.,  and it is also possible to carry out the step at a temperature  below about 20°  C.  It  is particularly preferable to carry out  the step in the coexistence of an acidic substance, because it  has a high effect of promoting the reaction and it allows a  later water treatment step to be carried out easily under an  acidic to neutral condition.  [0069]  The acidic substance is not limited to a particular  one. Organic acids include, for example, sulfonic acids such  as methanesulfonic acid, ethanesulfonic acid, p-toluene› sulfonic acid, o-, p- or m-nitrobenzenesulfonic acid; car› boxylic acids such as formic acid, acetic acid, trifluoroacetic  acid or benzoic acid. Inorganic acids include, for example,  hydrochloric acid, sulfuric acid, sulfurous acid, phosphoric  acid or the like. Also, in this reaction, leaving group L is  eliminated to produce secondarily a conjugate acid of the  leaving group L represented by the following general for› mula (7):  L-H  (7)  [0070]  wherein L is as defined above,  and the conjugate acid (7) of the leaving group Lis also used  as an acidic substance preferably.  [0071]  The amount of acidic substances used is not limited  to a particular range, and they are usually used in a molar  amount of0.01 to 100-fold, preferably in a molar amount of  0.05 to 50-fold, and more preferably in a molar amount of  0.1 to 20-fold, for example, relative to the N-protected-3- aminopropionic acid derivatives (3).  [0072]  Also, the basic substance is not limited to a par› ticular one, and weakly basic substances are preferably used.  The weakly basic substances are not limited to particular  ones. In general, basic substances showing a pKa value  below 10, for example, of the conjugate acid in an aqueous  solution are preferably used, and especially, those showing  a pKa value below 5 are more preferably used. Specific  examples include, for example, amines such as triethy› lamine, diisopropylamine or pyridine; carbonates such as  sodium carbonate or potassium carbonate; hydrogen carbon› ates such as sodium hydrogencarbonate or potassium hydro› gencarbonate. Organic solvents showing a weak basicity  such as N,N-dimethyl formamide, dimethyl sulfoxide or the  like are also within a range of selection.  [0073]  The amount of the basic substances used is not  limited to a particular range, and they are usually used in a  molar amount of 0.01 to 100-fold, preferably in a molar  amount of 0.05 to 50-fold, and more preferably in a molar  amount of 0.1 to 20-fold, for example, relative to the  N-protected-3-aminopropionic acid derivatives (3).  [0074]  In general, acidic substances are preferably used as  the above reaction accelerator, bacause they are easily  removed from the reaction mixture after completion of the  reaction and they have small influence in the yield and  quality of the products even if they are brought in the next  step as they are.  [0075]  Reaction solvents used in this reaction are not  limited to particular ones, and various solvents usually used  may be used. Examples of the reaction solvents include, for  example, aliphatic hydrocarbons such as hexane, heptane or  methylcyclohexane; aromatic 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 