4-[(2-fluorophenoxy)methyl]piperidine;hydrochloride

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

Procedure: After adding 150 mg of 5-chloromethyl-2,4-dihydro-[1,2,4]triazol-3-one, 331 mg of 4-(2-fluorophenoxymethyl)piperidine hydrochloride and 180 mg of anhydrous potassium carbonate to acetonitrile, the mixture was stirred overnight at room temperature. Water and ethyl acetate were added to the reaction mixture and the insoluble portion was filtered out to obtain the title compound (70 mg, 21% yield). the insoluble portion was filtered out

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

Procedure: After dissolving 221 mg of 2-tert-butoxy-4-vinylpyrimidine and 200 mg of 4-(2-fluorophenoxymethyl)piperidine hydrochloride in 5 ml of ethanol, 123 mg of anhydrous potassium carbonate was added and the mixture was heated to reflux for 50 minutes. Ethyl acetate was added to the reaction mixture, the insoluble portion was filtered off, and the filtrate was concentrated under reduced pressure. The residue was purified by NH silica gel column chromatography (solvent: n-hexane/ethyl acetate) to obtain the title compound (293 mg, 93% yield). was added the mixture was heated to reflux for 50 minutes the insoluble portion was filtered off the filtrate was concentrated under reduced pressure The residue was purified by NH silica gel column chromatography (solvent: n-hexane/ethyl acetate)

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

Procedure: After dissolving 221 mg of 2-tert-butoxy-4-vinylpyrimidine and 200 mg of 4-(2-fluorophenoxymethyl)piperidine hydrochloride in 5 ml of ethanol, 123 mg of anhydrous potassium carbonate was added and the mixture was heated to reflux for 50 minutes. Ethyl acetate was added to the reaction mixture, the insoluble portion was filtered off, and the filtrate was concentrated under reduced pressure. The residue was purified by NH silica gel column chromatography (solvent: n-hexane/ethyl acetate) to obtain the title compound (293 mg, 93% yield). was added the mixture was heated to reflux for 50 minutes the insoluble portion was filtered off the filtrate was concentrated under reduced pressure The residue was purified by NH silica gel column chromatography (solvent: n-hexane/ethyl acetate)

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

Procedure: After adding 139 mg of (Z)-2-tert-butoxy-3-(2-methoxyvinyl)pyrazine and 196 mg of 4-(2-fluorophenoxymethyl)piperidine hydrochloride in 5 ml of dichloromethane, 213 mg of sodium triacetoxyborohydride was added and the mixture was stirred overnight at room temperature. Aqueous sodium carbonate solution was added to the reaction mixture and extraction was performed with ethyl acetate. The organic layer was washed with water and saturated brine in that order and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (solvent: n-hexane/ethyl acetate) to obtain the title compound (26 mg, 10% yield). was added The organic layer was washed with water and saturated brine in that order dried over anhydrous magnesium sulfate the solvent was distilled off under reduced pressure The residue was purified by silica gel column chromatography (solvent: n-hexane/ethyl acetate)

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

Procedure: After adding 139 mg of (Z)-2-tert-butoxy-3-(2-methoxyvinyl)pyrazine and 196 mg of 4-(2-fluorophenoxymethyl)piperidine hydrochloride in 5 ml of dichloromethane, 213 mg of sodium triacetoxyborohydride was added and the mixture was stirred overnight at room temperature. Aqueous sodium carbonate solution was added to the reaction mixture and extraction was performed with ethyl acetate. The organic layer was washed with water and saturated brine in that order and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (solvent: n-hexane/ethyl acetate) to obtain the title compound (26 mg, 10% yield). was added The organic layer was washed with water and saturated brine in that order dried over anhydrous magnesium sulfate the solvent was distilled off under reduced pressure The residue was purified by silica gel column chromatography (solvent: n-hexane/ethyl acetate)

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

Procedure: After adding 150 mg of 5-chloromethyl-2,4-dihydro-[1,2,4]triazol-3-one, 331 mg of 4-(2-fluorophenoxymethyl)piperidine hydrochloride and 180 mg of anhydrous potassium carbonate to acetonitrile, the mixture was stirred overnight at room temperature. Water and ethyl acetate were added to the reaction mixture and the insoluble portion was filtered out to obtain the title compound (70 mg, 21% yield). the insoluble portion was filtered out

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

Procedure: After adding 139 mg of (Z)-2-tert-butoxy-3-(2-methoxyvinyl)pyrazine and 196 mg of 4-(2-fluorophenoxymethyl)piperidine hydrochloride in 5 ml of dichloromethane, 213 mg of sodium triacetoxyborohydride was added and the mixture was stirred overnight at room temperature. Aqueous sodium carbonate solution was added to the reaction mixture and extraction was performed with ethyl acetate. The organic layer was washed with water and saturated brine in that order and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (solvent: n-hexane/ethyl acetate) to obtain the title compound (26 mg, 10% yield). was added The organic layer was washed with water and saturated brine in that order dried over anhydrous magnesium sulfate the solvent was distilled off under reduced pressure The residue was purified by silica gel column chromatography (solvent: n-hexane/ethyl acetate)

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

Procedure: After adding 150 mg of 5-chloromethyl-2,4-dihydro-[1,2,4]triazol-3-one, 331 mg of 4-(2-fluorophenoxymethyl)piperidine hydrochloride and 180 mg of anhydrous potassium carbonate to acetonitrile, the mixture was stirred overnight at room temperature. Water and ethyl acetate were added to the reaction mixture and the insoluble portion was filtered out to obtain the title compound (70 mg, 21% yield). the insoluble portion was filtered out

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

Procedure: After adding 150 mg of 5-chloromethyl-2,4-dihydro-[1,2,4]triazol-3-one, 331 mg of 4-(2-fluorophenoxymethyl)piperidine hydrochloride and 180 mg of anhydrous potassium carbonate to acetonitrile, the mixture was stirred overnight at room temperature. Water and ethyl acetate were added to the reaction mixture and the insoluble portion was filtered out to obtain the title compound (70 mg, 21% yield). the insoluble portion was filtered out

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

Procedure: After dissolving 221 mg of 2-tert-butoxy-4-vinylpyrimidine and 200 mg of 4-(2-fluorophenoxymethyl)piperidine hydrochloride in 5 ml of ethanol, 123 mg of anhydrous potassium carbonate was added and the mixture was heated to reflux for 50 minutes. Ethyl acetate was added to the reaction mixture, the insoluble portion was filtered off, and the filtrate was concentrated under reduced pressure. The residue was purified by NH silica gel column chromatography (solvent: n-hexane/ethyl acetate) to obtain the title compound (293 mg, 93% yield). was added the mixture was heated to reflux for 50 minutes the insoluble portion was filtered off the filtrate was concentrated under reduced pressure The residue was purified by NH silica gel column chromatography (solvent: n-hexane/ethyl acetate)

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

Procedure: After dissolving 221 mg of 2-tert-butoxy-4-vinylpyrimidine and 200 mg of 4-(2-fluorophenoxymethyl)piperidine hydrochloride in 5 ml of ethanol, 123 mg of anhydrous potassium carbonate was added and the mixture was heated to reflux for 50 minutes. Ethyl acetate was added to the reaction mixture, the insoluble portion was filtered off, and the filtrate was concentrated under reduced pressure. The residue was purified by NH silica gel column chromatography (solvent: n-hexane/ethyl acetate) to obtain the title compound (293 mg, 93% yield). was added the mixture was heated to reflux for 50 minutes the insoluble portion was filtered off the filtrate was concentrated under reduced pressure The residue was purified by NH silica gel column chromatography (solvent: n-hexane/ethyl acetate)

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

Procedure: After adding 139 mg of (Z)-2-tert-butoxy-3-(2-methoxyvinyl)pyrazine and 196 mg of 4-(2-fluorophenoxymethyl)piperidine hydrochloride in 5 ml of dichloromethane, 213 mg of sodium triacetoxyborohydride was added and the mixture was stirred overnight at room temperature. Aqueous sodium carbonate solution was added to the reaction mixture and extraction was performed with ethyl acetate. The organic layer was washed with water and saturated brine in that order and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (solvent: n-hexane/ethyl acetate) to obtain the title compound (26 mg, 10% yield). was added The organic layer was washed with water and saturated brine in that order dried over anhydrous magnesium sulfate the solvent was distilled off under reduced pressure The residue was purified by silica gel column chromatography (solvent: n-hexane/ethyl acetate)