Hydrochloric Acid → (R)-(1-(5,6-Diaminopyridin-2-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone dihydrochloride

Participants

Reaction Conditions

Reaction Steps

Into a Parr bottle was added 10% palladium-on-carbon (50% wet, 1487.2 mg) followed by ethanol (10 mL) which was previously bubbled with nitrogen and cooled to 0° C. with an ice-water bath. (R)-(1-(6-Amino-5-nitropyridin-2-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone (10.612 g, 33.228 mmol) in ethanol (84 mL) was added into the Parr bottle followed by concentrated hydrochloric acid (8.59 mL, 99.6 mmol) dissolved in ethanol (10 mL) under a nitrogen atmosphere. The reaction mixture was purged with nitrogen and evacuated 3 times. The mixture was submitted to a hydrogen atmosphere (45 PSI). A drop in pressure was observed and it was increased to 46 PSI. This process was repeated several times over a period of 30 minutes. The reaction mixture was shaken for a total of 1 h. Then it was filtered through Celite and the residue was rinsed with ethanol (1 L). The solvent was removed under reduced pressure and the residue was redissolved in methanol. The solvent was removed under reduced pressure and the solid was dried under high vacuum to afford the title compound (12.0 g). The material was used without further purification. 1H NMR (400 MHz, CD3OD) δ 1.67-1.81 (m, 2H) 1.83-2.10 (m, 6H) 2.85-2.95 (m, 1H) 3.32-3.55 (m, 5H) 3.66 (dt, 1H) 3.89 (d, 1H) 3.97 (dd, 1H) 6.38 (d, 1H) 7.64 (d, 1H); MS (ES+) (M+H) 290.2.

Provenance & Evidence