[4-(piperidin-1-ylmethyl)phenyl]methanamine

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Use a method similar to the General Procedure)-2 to couple 7-chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethansulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (300 mg, 0.69 mmol) and 4-(piperidin-1-ylmethyl)-benzylamine (174 mg, 0.84 mmol). Purify by chromatography on silica gel (150 g) eluting with a gradient of DCM to 4:1 DCM/(chloroform:methanol:concentrated NH4OH 80:18:2) to obtain 7-chloro-6-[4-(piperidin-1-ylmethyl)-benzylamino]-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine as an oil (240 mg, 71%). MS (ES+) m/z: 480 (M+H)+. Purify by chromatography on silica gel (150 g) eluting with a gradient of DCM to 4:1 DCM/(chloroform:methanol:concentrated NH4OH 80:18:2)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Add 4-(piperidin-1-ylmethyl)-benzonitrile (890 mg, 4.45 mmol), 2M hydrogen chloride in ether (8.9 mL, 17.8 mmol) and 10% Pd/C (90 mg) to methanol (100 mL) in a pressure vessel. Flush the vessel three times with hydrogen and charge to 50 psi with hydrogen. Stir at room temperature for 2 h. Filter the catalyst through Celite® and concentrate the filtrate in vacuo. Purify by chromatography on silica gel (100 g) eluting with a gradient of DCM to 4:1 DCM/(chloroform:methanol:concentrated NH4OH 80:18:2) to obtain the title compound as a colorless oil (0.82 g, 90%). MS (ES+) m/z: 205 (M+H)+. Flush the vessel three times with hydrogen charge to 50 psi with hydrogen Filter the catalyst through Celite® concentrate the filtrate in vacuo Purify by chromatography on silica gel (100 g) eluting with a gradient of DCM to 4:1 DCM/(chloroform:methanol:concentrated NH4OH 80:18:2)