Реакция #1121754

Уравнение реакции

ammonium formate

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

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

→

pregabalin

Выход 81.0%

Растворители

MeOH

Условия реакции

Обработка

1. 1
   ДругоеAfter a few minutes an exothermic reaction
2. 2
   ДругоеThe catalyst was removed by filtration
3. 3
   КонцентрированиеThe 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
   Температураthe mixture was refluxed for 6 hours
7. 7
   КонцентрированиеAfter 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
    Другоеto crystallize
11. 11
    ТемператураWithin about 60 minutes the reaction mixture was cooled down to 10° C
12. 12
    workup.WAITwas continued for 1 hour
13. 13
    Другоеthe product was isolated by filtration
14. 14
    ПромывкаThe filter cake was washed with 90 mL of a 1:1 mixture of cold H2O/2-propanol
15. 15
    ДругоеAfter drying

Методика

(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%).

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