3-(Aminomethyl)-1-methylpiperidine synthesis

Yield: 35%

Reaction Conditions:

with sulfuric acid in 1,4-dioxane;methanol at 25; for 0.5 h;

Steps:

244.A A. 3-(AMINOMETHYL)-1-METHYLPIPERIDINE
3- (DI-TERT-BUTOXYCARBONYLAMINO)-1-METHYLPIPERIDINE (500mg, 1. 52mmoles) (from Preparative Example 244, Step B above) was dissolved in methanol (7.5mL) and 10% (v/v) CONC. sulfuric acid in 1,4-dioxane (19. 75mL) was added. The solution was stirred at 25 C for 0. 5H. Methanol (300mL) was added, followed by BioRad AG1-X8 resin (OH FORM) until the pH was-10. The resin was filtered off and washed with METHANOL (2X200ML). The combined eluates were evaporated to dryness and the residue was chromatographed on a silica gel column (30x2.5cm) using 10% (10% CONC. ammonium hydroxide in METHANOL)-DICHLOROMETHANE as the eluant to give 3-(aminomethyl)-1- methylpiperidine (69.2mg, 35%): FABMS: m/z 129.1 (MH+) ; HRFABMS: m/z 129.1392 (MH+). CALCD. FOR C7H17N2 : m/z 129. 1392 ; 8H (CDC13) 0.90 (2H, m, CH2), 1.65 (2H, m, CH2), 1.72 (1 H, M, CH), 1.79 (1H, m, CH2), 1. 91 (1H, m, CH2), 2.30 (3H, s,-NCH3), 2.64 (2H, m, CH2), 2.82 (1 H, M,-CH2NH2) and 2.92 ppm (1 H, M,-CH2NH2) ; 8c (CDCl3) CH3 : 46.7 ; CH2 : 25.2, 28.0, 46. 3, 56.4, 60.3 ; CH: 39.9.

References:

SCHERING CORPORATION;PHARMACOPEIA, INC. WO2004/22561, 2004, A1 Location in patent:Page 109