Reacción #1121754

Ecuación de reacción

ammonium formate

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

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

→

pregabalin

Rendimiento 81.0%

Disolventes

MeOH

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroAfter a few minutes an exothermic reaction
2. 2
   OtroThe catalyst was removed by filtration
3. 3
   ConcentraciónThe 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
   Temperaturathe mixture was refluxed for 6 hours
7. 7
   ConcentraciónAfter 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
    Otroto crystallize
11. 11
    TemperaturaWithin about 60 minutes the reaction mixture was cooled down to 10° C
12. 12
    workup.WAITwas continued for 1 hour
13. 13
    Otrothe product was isolated by filtration
14. 14
    LavadoThe filter cake was washed with 90 mL of a 1:1 mixture of cold H2O/2-propanol
15. 15
    OtroAfter drying

Procedimiento

(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%).

Fuente