4-(4-PIPERIDINYLMETHYL)BENZAMIDE synthesis

Yield:333795-12-3 86.1%

Reaction Conditions:

with hydrogen;palladium 10% on activated carbon in methanol at 50; for 3 - 5 h;Product distribution / selectivity;

Steps:

4; 5 Production of 4-(4-piperidylmethyl)benzamide

The compound (4267.9 g, 13.929 mol) obtained in Example 3, 10% palladium carbon (889.4 g, ca. 50% water-containing product) and methanol (38.4 L) were charged, and a hydrogenation reaction was conducted at normal pressure at 50°C for 5 hrs. After the reaction, the reaction mixture was separated by filtration without cooling to remove the insoluble material and washed with methanol (3 L). The reaction mixture was concentrated under reduced pressure to about 10 L, and ethyl acetate (15 L) was added, followed by concentration again under reduced pressure to about 10 L, which step was conducted twice. The residue (ca. 10 L) was stirred under reflux for 2 hrs., and cooled to room temperature. The crystals were collected by filtration, washed with ethyl acetate (2 L) and dried in vacuo at 40°C to give the title compound (2619.2 g, yield 86.1%) as white crystals. ¹H-NMR (300MHz, CDCl₃)δ: 1.14-1.19(2H,m), 1.59-1.63(3H,m), 2.49-2.59(4H,m), 3.03-3.07(2H,m), 7.21-7.75(4H,m).; Example 5Production of 4-(4-piperidylmethyl)benzamide The compound (0.919 g, 3.00 mmol) obtained in Reference Example 1, 10% palladium carbon (0.192 g, ca. 50% water-containing product) and methanol (9.2 mL) were charged, and the mixture was stirred vigorously under hydrogen atmosphere at 50°C for 3 hrs. Insoluble materials were filtered off, and the residue was washed with methanol (2.0 mL) and concentrated under reduced pressure to give the title compound (0.642g, yield 98%) as a white dry solid.1H-NNR (300MHz, CDCl3)δ: 1.14-1.19(2H,m), 1.59-1.63(3H,m), 2.49-2.59(4H,m), 3.03-3.07(2H,m), 6.10(2H,br.s,NH2), 7.21-7.75(4H,m).

References:

EP1359145,2003,A1 Location in patent:Page/Page column 28-29