Formaldehyde → 1-Methylpiperidine-4-carboxamide

Isonipecotamide (10 g, 78.0 mmoles) was dissolved in distilled water (100 mL) and 37% aqueous formaldehyde (7.6 mL, equivalent to 2.81 g HCHO, 93.6 mmoles) was added. Wet 10% Pd—C (8 spoon spatulas) was added under argon and the mixture was hydrogenated at 25° C. and 50 psi for 43 h. The catalyst was filtered off through Celite and the latter was washed with water and methanol. The combined filtrates were evaporated to dryness and the residue was chromatographed on a silica gel column (60×5 cm) using 8%-10%-20% (10% conc. ammonium hydroxide in methanol)-dichloromethane as the eluant to give 1-methylisonipecotamide (7.15 g, 64%): FABMS: m/z 143.1 (MH+); HRFABMS: m/z 143.1184 (MH+). Calcd. for C7H15N2O: m/z 143.1184; δH (d6-DMSO) 1.50/1.57 (4H, m, CH2), 1.76/1.94 (4H, m, CH2), 2.10 (3H, s, —NCH3), 2.72 (1H, m, CH) and 6.68/7.18 ppm (2H, m, CONH2); δC (d6-DMSO)CH3: 41.2; CH2: 28.5, 28.5, 54.9, 54.9; CH: 46.2; C: 176.7.

1. customwas hydrogenated at 25° C.
2. filtrationThe catalyst was filtered off through Celite
3. washthe latter was washed with water and methanol
4. customThe combined filtrates were evaporated to dryness
5. customthe residue was chromatographed on a silica gel column (60×5 cm)

ORD record

ord-870d07e9090946d18092e0328141bc87

Source dataset

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08673924B2