1-(2,2-difluoroethyl)piperidin-4-amine;dihydrochloride

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

Procedure: To a mixture of 1.07 g (3.78 mmole) of 4-amino-3-methoxy-benzoic acid benzotriazol-1-yl ester, 0.90 g (3.78 mmole) of 1-(2,2-difluoro-ethyl)-piperidin-4-ylamine dihydrochloride and 5 mL of dimethylformamide was added 2.63 mL of triethylamine. The mixture was stirred for 20 hours, then taken up in dichloromethane and washed twice with 100 mL of saturated aqueous sodium bicarbonate, once with 50 mL water, once with 50 mL brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with dichloromethane-methanol (gradient, 100:0-90:10) to give 1.05 g of 4-amino-N-[1-(2,2-difluoro-ethyl)-piperidin-4-yl]-3-methoxy-benzamide. washed twice with 100 mL of saturated aqueous sodium bicarbonate, once with 50 mL water, once with 50 mL brine dried over anhydrous sodium sulfate filtered concentrated under reduced pressure The residue was purified by silica gel chromatography eluting with dichloromethane-methanol (gradient, 100:0-90:10)

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

Procedure: To a cooled (0 degrees) mixture of 1.21 g (4.58 mmole) of [1-(2,2-difluoro-ethyl)-piperidin-4-yl]-carbamic acid tert-butyl ester and 20 mL of dioxane, was added 5.7 mL of 4M HCl in dioxane. The mixture was stirred at room temperature overnight, and the solid collected by filtration to give 0.90 g of 1-(2,2-difluoro-ethyl)-piperidin-4-ylamine dihydrochloride. To a cooled the solid collected by filtration