piperidin-4-ylmethanol;hydrochloride

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1-(2-chloroethyl)-1,3-dihydro-3-(1-methylethyl)-2H-imidazol-2-one (12 g), 4-piperidinemethanol hydrochloride (9.1 g), N,N-diethylethanamine (21 ml) and KI (catalytic amount) in DMF (200 ml) was stirred for 20 hours at 70° C. The reaction mixture was cooled and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH/NH3) 95/5). The pure fractions were collected and the solvent was evaporated, yielding 6.9 g (43%) 1,3-dihydro-1-[2-[4-(hydroxymethyl)-1-piperidinyl]ethyl]-3-(1-methylethyl)-2H-imidazol-2-one (intermediate 3). The reaction mixture was cooled the solvent was evaporated The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH/NH3) 95/5) The pure fractions were collected the solvent was evaporated

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1-(2-chloroethyl)-1,3-dihydro-3-(1-methylethyl)-2H-imidazol-2-one (12 g), 4-piperidinemethanol hydrochloride (9.1 g), N,N-diethylethanamine (21 ml) and KI (catalytic amount) in DMF (200 ml) was stirred for 20 hours at 70° C. The reaction mixture was cooled and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH/NH3) 95/5). The pure fractions were collected and the solvent was evaporated, yielding 6.9 g (43%) 1,3-dihydro-1-[2-[4-(hydroxymethyl)-1-piperidinyl]ethyl]-3-(1-methylethyl)-2H-imidazol-2-one (intermediate 3). The reaction mixture was cooled the solvent was evaporated The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH/NH3) 95/5) The pure fractions were collected the solvent was evaporated

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1-(2-chloroethyl)-1,3-dihydro-3-(1-methylethyl)-2H-imidazol-2-one (12 g), 4-piperidinemethanol hydrochloride (9.1 g), N,N-diethylethanamine (21 ml) and KI (catalytic amount) in DMF (200 ml) was stirred for 20 hours at 70° C. The reaction mixture was cooled and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH/NH3) 95/5). The pure fractions were collected and the solvent was evaporated, yielding 6.9 g (43%) 1,3-dihydro-1-[2-[4-(hydroxymethyl)-1-piperidinyl]ethyl]-3-(1-methylethyl)-2H-imidazol-2-one (intermediate 3). The reaction mixture was cooled the solvent was evaporated The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH/NH3) 95/5) The pure fractions were collected the solvent was evaporated

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 168.3 g (1.22 mol) of potassium carbonate are added to a solution of 61.6 g (406 mmol) of 4-piperidinemethanol hydrochloride in a mixture of 406 ml of chloroform and 406 ml of water, followed by 42.55 ml (440 mmol) of ethyl chloroformate dissolved in 160 ml of chloroform. The mixture is stirred for 3 h at 20° C., the organic phase is separated off, the aqueous phase is extracted with dichloromethane, the organic phases are combined to form a single phase, washed with water and dried over magnesium sulphate, and the solvents are evaporated off under reduced pressure. 76 g of an oil is obtained, this being used without further treatment in the following stage. the organic phase is separated off the aqueous phase is extracted with dichloromethane to form a single phase washed with water dried over magnesium sulphate the solvents are evaporated off under reduced pressure

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

Procedure: 105 g of 1-benzyl-4-piperidinemethanol hydrochloride, 2 l of ethanol and 12.5 g of palladinized charcoal are introduced into a Parr bottle, and a hydrogenolysis is performed at 50° C. under a pressure of 0.4 MPa. The mixture is filtered and the filtrate evaporated off under reduced pressure. 58.7 g of solid are obtained. Melting point: 128°-130° C. is performed at 50° C. under a pressure of 0.4 MPa The mixture is filtered the filtrate evaporated off under reduced pressure

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

Procedure: In 20 ml of N,N-dimethylformamide, 2.291 g (15.108 mM) of 4-piperidylmethanol hydrochloride, 4.48 g (18.1 mM) of bromodiphenylmethane, and 6.26 g (45.3 mM) of potassium carbonate were stirred together at 100° C. for 3.5 days and, then, at 150° C. for 2 hours. After cooling to room temperature, this reaction mixture was poured in water and extracted with 2 portions of ethyl acetate. The organic layers were pooled and dried over MgSO4 and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=3/1 to 2/1 to 1/1) to provide the title compound. extracted with 2 portions of ethyl acetate dried over MgSO4 the solvent was distilled off under reduced pressure The residue was purified by silica gel column chromatography (hexane/ethyl acetate=3/1 to 2/1 to 1/1)

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

Procedure: A solution of 12.2 g of 4-hydroxymethyl-piperidine-hydrochloride, 9.8 g of 4-fluorobenzonitrile and 28.3 ml of N-ethyl-diisopropylamine is heated to 140° C. for 4 hours. After cooling, it is chromatographed over silica gel using methylene chloride and methylene chloride/ethyl acetate (1:1) as eluant. After the solvent has been removed under reduced pressure the residue remaining is triturated with petroleum ether and suction filtered. Yield: 5.1 g (29% of theory), Melting point: 148°-150° C. After cooling it is chromatographed over silica gel After the solvent has been removed under reduced pressure the residue remaining is triturated with petroleum ether and suction filtered

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1-(2-chloroethyl)-1,3-dihydro-3-(1-methylethyl)-2H-imidazol-2-one (12 g), 4-piperidinemethanol hydrochloride (9.1 g), N,N-diethylethanamine (21 ml) and KI (catalytic amount) in DMF (200 ml) was stirred for 20 hours at 70° C. The reaction mixture was cooled and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH/NH3) 95/5). The pure fractions were collected and the solvent was evaporated, yielding 6.9 g (43%) 1,3-dihydro-1-[2-[4-(hydroxymethyl)-1-piperidinyl]ethyl]-3-(1-methylethyl)-2H-imidazol-2-one (intermediate 3). The reaction mixture was cooled the solvent was evaporated The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH/NH3) 95/5) The pure fractions were collected the solvent was evaporated

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1-(2-chloroethyl)-1,3-dihydro-3-(1-methylethyl)-2H-imidazol-2-one (12 g), 4-piperidinemethanol hydrochloride (9.1 g), N,N-diethylethanamine (21 ml) and KI (catalytic amount) in DMF (200 ml) was stirred for 20 hours at 70° C. The reaction mixture was cooled and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH/NH3)95/5). The pure fractions were collected and the solvent was evaporated, yielding 6.9 g (43%) 1,3-dihydro-1-[2-[4-(hydroxymethyl)-1-piperidinyl]ethyl]-3-(1-methylethyl)-2H-imidazol-2-one (intermediate 3). The reaction mixture was cooled the solvent was evaporated The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH/NH3)95/5) The pure fractions were collected the solvent was evaporated

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1-(2-chloroethyl)-1,3-dihydro-3-(1-methylethyl)-2H-imidazol-2-one (12 g), 4-piperidinemethanol hydrochloride (9.1 g), N,N-diethylethanamine (21 ml) and KI (catalytic amount) in DMF (200 ml) was stirred for 20 hours at 70° C. The reaction mixture was cooled and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH/NH3) 95/5). The pure fractions were collected and the solvent was evaporated, yielding 6.9 g (43%) 1,3-dihydro-1-[2-[4-(hydroxymethyl)-1-piperidinyl]ethyl]-3-(1-methylethyl)-2H-imidazol-2-one (intermediate 3). The reaction mixture was cooled the solvent was evaporated The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH/NH3) 95/5) The pure fractions were collected the solvent was evaporated