Potassium Hydroxide → Pregabalin

Temperature

10 °C

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%).

1. customThe initially turbid reaction mixture
2. filtrationThe solution was filtered
3. concentrationconcentrated to about 250 g under reduced pressure and 400 mL of 2-propanol
4. additionwere added
5. additionAt a temperature of 45° C. acetic acid was added until a pH of 7.0
6. customto crystallize
7. stirringStirring
8. customthe product was isolated by filtration
9. washThe filter cake was washed with 90 mL of a 1:1 mixture of cold H2O/2-propanol
10. customAfter drying

ORD record

ord-d6a39975a66949c7a147349cb1adb027

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08546112B2