反応 #1121754

反応方程式

ammonium formate

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

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

→

pregabalin

収率 81.0%

溶媒

MeOH

反応条件

後処理

1. 1
   その他After a few minutes an exothermic reaction
2. 2
   その他The catalyst was removed by filtration
3. 3
   濃縮The filtrate was concentrated under reduced pressure to a volume of about 20 mL
4. 4
   workup.ADDITIONWater (20 mL) was added
5. 5
   workup.ADDITIONThen 50 mL of 6N aqueous HCl were added
6. 6
   温度the mixture was refluxed for 6 hours
7. 7
   濃縮After complete conversion, the reaction mixture was concentrated under reduced pressure to about 20 mL
8. 8
   workup.ADDITIONWater (20 mL) and 2-propanol (40 mL) were added
9. 9
   workup.ADDITIONKOH was added until a pH of 7
10. 10
    その他to crystallize
11. 11
    温度Within about 60 minutes the reaction mixture was cooled down to 10° C
12. 12
    workup.WAITwas continued for 1 hour
13. 13
    その他the product was isolated by filtration
14. 14
    洗浄The filter cake was washed with 90 mL of a 1:1 mixture of cold H2O/2-propanol
15. 15
    その他After drying

実験手順

(S)-5-Methyl-3-nitromethyl-hexanoic acid ethyl ester (VIII, R1=ethyl) (10.4 g) were dissolved in 160 mL of MeOH. 4 g of 10% Pd/C and 20 g of ammonium formate were added. After a few minutes an exothermic reaction was observed. After 30 minutes HPLC analysis indicated complete conversion. The catalyst was removed by filtration. The filtrate was concentrated under reduced pressure to a volume of about 20 mL. Water (20 mL) was added, then the solution was again concentrated unter reduced pressure to about 20 mL. Then 50 mL of 6N aqueous HCl were added and the mixture was refluxed for 6 hours. After complete conversion, the reaction mixture was concentrated under reduced pressure to about 20 mL. Water (20 mL) and 2-propanol (40 mL) were added and the reaction mixture was heated to 45° C. KOH was added until a pH of 7 was reached. The product 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, 5.9 g of substantially pure pregabalin (purity 98.0%) were obtained (yield: 81%).

出典