Jun.22,2006  15  US 2006/0135784 Al  Example 4  Conversion of (2S,3S)-3-( ethoxycarbonyl)amino-2- hydroxy-4-phenylbutyric acid into (2S,3S)-3- ( ethoxycarbony l)-amino-2-methanesulfonyloxy-4- pheny lbutyric acid methyl ester  Example 6  Conversion of (2S,3S)-3-( ethoxycarbonyl)amino-2- hydroxy-4-phenylbutyric acid through 3-( ethoxycar› bonyl)amino-2-chloro-4-phenylbutyric acid into  (2R,3S)-3-amino-2-hydroxy-4-phenylbutyric acid  Example 7  Conversion of 3-( ethoxycarbonyl)amino-2-hydroxy- 4-phenylbutyric acid (diastereomer mixture) into  3-( ethoxycarbonyl )-amino-2-methanesulfony loxy-4- phenylbutyric acid methyl ester  Example 5  Conversion of (2S,3S)-3-( ethoxycarbonyl)amino-2- methanesulfonyloxy-4-phenylbutyric acid methyl  ester into (2R,3S)-3-amino-2-hydroxy-4-phenylbu- tyric acid  [0159]  Thionyl chloride (596 mg) was added to methanol  (1.39 g) over 10 minutes under ice-cooling, and the mixture  was reacted at the same temperature for 1 hour. The resultant  solution was added to a solution of (2S,3S)-3-(ethoxycar› bonyl)amino-2-hydroxy-4-phenylbutyric acid (HPLC area  ratio of erythro-isomer/threo-isomer=99/1) (1.04 g) and  toluene (10 ml) over 10 minutes under ice-cooling. The  mixture was reacted at the same temperature for 2 hours and  then warmed to room temperature. From the resultant reac› tion solution, methanol and thionyl chloride as well as  components secondarily produced from these reagents and  having a low boiling point such as sulfurous acids hydrogen  chloride or the like were distilled off under reduced pressure.  Tetrahydrofuran was added to the resultant residue to obtain  a tetrahydrofuran solution (10.12 g) of (2S,3S)-3-(ethoxy› carbonyl)amino-2-hydroxy-4-phenylbutyric  acid  methyl  ester. The HPLC area ratio of erythro-isomer/threo-isomer  was 99/1, and the diastereomer excess was 99% d.e.  [0160]  To the tetrahydrofuran solution (5.04 g) of (2S,3S)- 3-( ethoxycarbony l)amino-2-hydroxy-4-pheny lbutyric  acid  methyl ester thus obtained, triethylamine ( 421 mg) was  added under ice-cooling. Then, methanesulfony chloride  (1376 mg) was added to the mixture over 10 minutes, and  the mixture was reacted at the same temperature for 2 hours.  Toluene (5 ml) and water (5 ml) were added to the resultant  reaction solution, and the aqueous phase was separated. The  resultant organic phase was concentrated under reduced  pressure  to  obtain  (2S,3S)-3-( ethoxycarbonyl)amino-2- methanesulfonyloxy-4-phenylbutyric  acid  methyl  ester  (erythro-isomer) (685 mg) as a white solid. The HPLC area  ratio of erythro-isomer/threo-isomer was 99/1, and the dias› tereomer excess was 99% d.e.  [0161]  $^{1}$H-NMR Spectra (CDC1$_{3}$ ,  TMS internal standard)  of the resultant (2S,3S)-3-( ethoxycarbonyl)amino-2-meth› anesulfonyloxy-4-phenylbutyric acid methyl ester were:  Ii  1.19 (3H, t,  1=7.2  Hz), 2.79-2.86 (2H, m), 3.20 (3H, s), 3.64  (3H, s), 4.08 (2H, q,  1=7.2  Hz), 4.55-4.63 (lH, m), 4.92 (lH,  d, 1=8.8 Hz), 5.31 (lH, brs), 7.17-7.33 (5H, m).  [0162]  Also, $^{13}$C NMR spectra (CDC1$_{3}$) were:  Ii  14.4,  35.6, 39.2, 52.8, 53.0, 61.3, 78.61 127.1, 128.6, 129.3,  135.9, 155.8, 167.4.  solution of sodium hydroxide (551 mg) were added to the  resultant residue, and the mixture was reacted at 60°  C. for  15 hours. Determination by HPLC revealed that the amount  of (2R,3S)-3-amino-2-hydroxy-4-phenylbutyric acid (threo› isomer) in the resultant reaction solution was 71 mg. Also,  (2S,3S)-3-amino-2-hydroxy-4-phenylbutyric acid ( erythro› isomer) was not detected.  [0164]  Thionyl chloride (694 mg) was added to a solution  of (2S,3S)-3-( ethoxycarbonyl)amino-2-hydroxy-4-phenyl› butyric acid (HPLC area ratio of erythro-isomer/threo-iso› mer=99/1) (277 mg) and tetrahydrofuran (2 ml) over 2 hours  under ice-cooling, and the temperature of the mixture was  then raised to 60°  C. stepwise. The mixture was reacted at  60°  C. for 24 hours. From the resultant reaction solution,  tetrahydrofuran and thionyl chloride as well as components  secondarily produced from thionyl chloride and having a  low boiling point such as sulfurous acid, hydrogen chloride  or the like were distiled off under reduced pressure. The  resultant residue was treated with a silica gel colunm (silica  gel: WAKOGEL C-200, developing solvent: ethyl acetate/  hexane=30/70) to  obtain a concentrate (100 mg) of  3-( ethoxycarbonyl)amino-2-chloro-4-phenylbutyric acid as  a solid.  [0165]  LC/MS Spectra (ESI) of the resultant 3-(ethoxy› carbonyl)amino-2-chloro-4-phenylbutyric acid were: m/e  286.1 [100%, M(Cl$^{35}$)+1], 288.2 [36%, M(Cl$^{37}$)+1].  [0166]  The concentrate (73 mg) thus obtained was dis› solved in N,N-dimethyl formamide (1 ml), and the mixture  was reacted at 100°  C. for 2 days. The resultant reaction  solution was concentrated under reduced pressure, water  (0.4 ml) and a 30% aqueous solution of sodium hydroxide  (0.4 ml) were added to the resultant residue, and the mixture  was reacted at 60°  C. for 18 hours. Determination by HPLC  revealed that the amount of the (2R,3S)-3-amino-2-hydroxy- 4-phenylbutyric acid in the resultant reaction solution was  46 mg. Also, the HPLC area ratio of threo-isomer/erythro› isomer was 97/3, and the diastereomer excess was 94% d.e.  [  0163]  (2S,3S )-3-Ethoxycarbony l)amino-2-methanesulfo› ny loxy-4-pheny lbutyric acid methyl ester (HPLC area ratio  of erythro-isomer/threo-isomer=99/1) (148 mg) obtained in  Example 4 was dissolved in N,N-dimethyl formamide (3  ml), the temperature of the mixture was gradually raised  from 60°  C., and the mixture was reacted finally at 100°  C.  for 8 hours. The resultant reaction solution was concentrated  under reduced pressure, water (2 ml) and a 30% aqueous  [0167]  Thionyl chloride (3.46 g) was added to methanol  (2.64 g) over 30 minutes under ice-cooling, and the mixture  was reacted at the same temperature for 1 hour. The resultant  solution was added to a toluene solution (54.51 g) containing  the diastereomer mixture ( 4.05 g) of 3-( ethoxycarbony› l)amino-2-hydroxy-4-phenylbutyric  acid  obtained  in  Example 2 (HPLC area ratio of erythro-isomer/threo-iso› mer=83/17, diastereomer excess=66% d.e.) over 30 minutes  under ice-cooling. The mixture was reacted at the same  temperature for 2 hours, and the temperature of the mixture  was then raised to room temperature. From the resultant  reaction solution, methanol and thionyl chloride as well as 