Ammonia → 3-(Piperidin-4-yl)propanoic acid

Temperature

30 °C

3-(4-pyridine)acrylic acid (18 kg) was added to 75 kg of water. The resulting suspension was stirred and neutralized (pH 7.5) with 6.8 kg of aqueous ammonia (25%). A slurry of Rh/Al2O3 (0.9 kg) in 5 kg of water was added to the reaction mixture, which was then made inert under nitrogen. The mixture was hydrogenated under a pressure of 3-3.5 bar at 85-95° C. After eight hours, when no further change in pressure was observed, the mixture was cooled to 25-35° C. The catalyst was filtered and washed with 4.0 kg of water. Ammonia and most of the water in the reaction mixture were removed under vacuum at 80-90° C., and the product began to precipitate. Acetonitrile (116 kg) was added and then the mixture was concentrated (ca. 50%) under vacuum. Additional acetonitrile (57.1 kg) was added to aid in crystallization and the reaction mixture was stirred for 1-4 hours at 15-25° C. until precipitation of the product was complete. The product was centrifuged and oven dried under vacuum at 45-55° C. to afford 19.1 kg (100%) of the title compound.

1. customwas hydrogenated under a pressure of 3-3.5 bar at 85-95° C
2. filtrationThe catalyst was filtered
3. washwashed with 4.0 kg of water
4. customAmmonia and most of the water in the reaction mixture were removed under vacuum at 80-90° C.
5. customto precipitate
6. additionAcetonitrile (116 kg) was added
7. concentrationthe mixture was concentrated (ca. 50%) under vacuum
8. additionAdditional acetonitrile (57.1 kg) was added to aid in crystallization
9. stirringthe reaction mixture was stirred for 1-4 hours at 15-25° C. until precipitation of the product
10. customoven dried under vacuum at 45-55° C.

ORD record

ord-448a411cf8814b9087fbeb001a62787a

Source dataset

uspto-grants-2003_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06515130B1