反応 #1121751

反応方程式

(S)-5-methyl-3-nitromethyl-hexanoic acid ethyl ester

KOH

→

pregabalin

収率 61.0%

溶媒

H2O

反応条件

後処理

1. 1
   その他The initially turbid reaction mixture
2. 2
   ろ過The solution was filtered
3. 3
   濃縮concentrated to about 250 g under reduced pressure and 400 mL of 2-propanol
4. 4
   workup.ADDITIONwere added
5. 5
   workup.ADDITIONAt a temperature of 45° C. acetic acid was added until a pH of 7.0
6. 6
   その他to crystallize
7. 7
   workup.STIRRINGStirring
8. 8
   その他the product was isolated by filtration
9. 9
   洗浄The filter cake was washed with 90 mL of a 1:1 mixture of cold H2O/2-propanol
10. 10
    その他After drying

実験手順

150 g of (S)-5-methyl-3-nitromethyl-hexanoic acid ethyl ester (VIII, R1=ethyl; assay: 97.2%) were suspended in 300 mL of H2O. KOH (90.1.g, assay 86.1%, 2.05 eq.) was added. The initially turbid reaction mixture became clear which indicated that the reaction was nearly completed. After complete conversion (determined by HPLC) NH4-formate and Pd/C were added. The reaction mixture was stirred until complete conversion was observed. The solution was filtered and then concentrated to about 250 g under reduced pressure and 400 mL of 2-propanol were added. At a temperature of 45° C. acetic acid was added until a pH of 7.0 was reached. Pregabalin started to crystallize. Within about 60 minutes the reaction mixture was cooled down to 10° C. Stirring was continued for 1 hour, then the product was isolated by filtration. The filter cake was washed with 90 mL of a 1:1 mixture of cold H2O/2-propanol. After drying, 65 g of substantially pure pregabalin (purity 97.9%) were obtained (yield: 61%).

出典