4-(2-chloroethyl)-1,2-dimethoxybenzene

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: The same procedure as that of Example 1 (1) to (8) was repeated except that 2-(3-pyridyl)ethyl chloride hydrochloride was replaced with 3,4-dimethoxyphenethyl chloride to prepare the intended compound. to prepare the intended compound

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

Procedure: A mixture of 5.75 g of 3-(hydroxymethyl)piperidine, 13.8 ml of triethylamine and 10 g of 2-(3,4-dimethoxyphenyl)-ethyl chloride was heated under reflux for 4 hours. After the reaction mixture had cooled, it was acidified with about 30 ml of aqueous 2N hydrochloric acid solution, and unreacted 2-(3,4-dimethoxyphenyl)-ethyl chloride was separated by extraction with tert-butyl methyl ether. The aqueous phase was then rendered alkaline by addition of sodium hydroxide solution and was extracted with dichloromethane. The organic phase was separated, dried and concentrated. 5.3 g of N-[2-(3,4-dimethoxyphenyl)-ethyl]-3-(hydroxymethyl)-piperidine were obtained. was heated under reflux for 4 hours After the reaction mixture had cooled was separated by extraction with tert-butyl methyl ether by addition of sodium hydroxide solution was extracted with dichloromethane The organic phase was separated dried concentrated

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

Procedure: A mixture of 5.75 g of 3-(hydroxymethyl)piperidine, 13.8 ml of triethylamine and 10 g of 2-(3,4-dimethoxyphenyl)-ethyl chloride was heated under reflux for 4 hours. After the reaction mixture had cooled, it was acidified with about 30 ml of aqueous 2N hydrochloric acid solution, and unreacted 2-(3,4-dimethoxyphenyl)-ethyl chloride was separated by extraction with tert-butyl methyl ether. The aqueous phase was then rendered alkaline by addition of sodium hydroxide solution and was extracted with dichloromethane. The organic phase was separated, dried and concentrated. 5.3 g of N-[2-(3,4-dimethoxyphenyl)-ethyl]-3-(hydroxymethyl)-piperidine were obtained. was heated under reflux for 4 hours After the reaction mixture had cooled was separated by extraction with tert-butyl methyl ether by addition of sodium hydroxide solution was extracted with dichloromethane The organic phase was separated dried concentrated

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

Procedure: 6.03 g of the hydrochloride was suspended into 100 ml of acetonitrile, to which 4.79 g of 2-(3,4-dimethoxyphenyl) ethyl chloride, 8.24 g of anhydrous potassium carbonate and n-tetrabutyl ammonium iodide (catalytic amount) were added and refluxed under heating for 20 hours. After allowing them to cool, the inorganic salts were filtered out and the solvent was distilled off. After adding ethyl acetate and washed with water, they were dried with anhydrous magnesium sulfate. The solvent was concentrated and purified on silica gel chromatography to obtain 1.03 g of the above-captioned compound (total yield: 6.5%). were added refluxed under heating for 20 hours to cool the inorganic salts were filtered out the solvent was distilled off After adding ethyl acetate washed with water, they were dried with anhydrous magnesium sulfate The solvent was concentrated purified on silica gel chromatography

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

Procedure: 32.27 g of homopiperazine, 13.2 g of 2-(3,4-dimethoxyphenyl)ethyl chloride and 71.3 g of potassium carbonate were added to 500 ml of acetonitrile. The obtained mixture was heated under reflux for 20 hours, cooled and filtered. The filtrate was concentrated under a reduced pressure to obtain a residue. This residue was extracted with ether thrice. The extracts were combined, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under a reduced pressure. The obtained residue was purified by silica gel column chromatography (solvent: chloroform/methanol/isopropylamine (100:10:1)) to obtain 13.40 g of the title compound as a yellow oil (yield: 77%). The obtained mixture was heated under reflux for 20 hours cooled filtered The filtrate was concentrated under a reduced pressure to obtain a residue This residue was extracted with ether thrice dried over anhydrous sodium sulfate filtered The filtrate was concentrated under a reduced pressure The obtained residue was purified by silica gel column chromatography (solvent: chloroform/methanol/isopropylamine (100:10:1))

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A reaction mixture of 4-(2-chloroethyl)-1,2-dimethoxybenzene (3.6 g, 17.9 mmol), piperazine-1-carboxylic acid t-butyl ester (4.0 g, 21.5 mmol), K2CO3 (4.97 g, 36 mmol), and NaI (2.7 g, 18 mmol) in DMF (20 mL) was stirred at 80° C. for 3 h, cooled to room temperature, and partitioned between water and ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous sodium sulfate, and concentrated. The residue was purified by column chromatography to afford 4-[2-(3,4-dimethoxy-phenyl)-ethyl]-piperazine-1-carboxylic acid t-butyl ester (4.8 g, 76%) which was dissolved in 4 N HCl in dioxane. This solution was stirred at room temperature for 4 h, concentrated, and dried in a high vacuum oven to give the title compound quantitatively. cooled to room temperature partitioned between water and ethyl acetate The organic layer was washed with water and brine dried over anhydrous sodium sulfate concentrated The residue was purified by column chromatography

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

Procedure: The reaction mixture of 2-(3,4-dimethoxyphenyl)ethanol (6.0 g, 32.8 mmol) and thionyl chloride (19 g, 164 mmol) in chloroform (20 mL) was stirred at reflux for 4 h, concentrated, and partitioned between water and ethyl acetate. The organic layer was washed with NaHCO3 and brine, dried over anhydrous sodium sulfate, and concentrated to afford 4-(2-chloroethyl)-1,2-dimethoxybenzene (K) quantitatively (6.6 g). at reflux for 4 h concentrated partitioned between water and ethyl acetate The organic layer was washed with NaHCO3 and brine dried over anhydrous sodium sulfate concentrated

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

Procedure: The reaction mixture of 2-(3,4-dimethoxyphenyl)ethanol (6.0 g, 32.8 mmol) and thionyl chloride (19 g, 164 mmol) in chloroform (20 mL) was stirred at reflux for 4 h, concentrated, and partitioned between water and ethyl acetate. The organic layer was washed with NaHCO3 and brine, dried over anhydrous sodium sulfate, and concentrated to afford 4-(2-chloroethyl)-1,2-dimethoxybenzene (K) quantitatively (6.6 g). at reflux for 4 h concentrated partitioned between water and ethyl acetate The organic layer was washed with NaHCO3 and brine dried over anhydrous sodium sulfate concentrated

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

Procedure: 42.8 Grams (0.32 moles) of aluminum chloride was added in portions to a solution of 45.9 g. (0.2 mole) of homoveratryl chloride and benzene (25 ml.) in methylene chloride (300 ml.). The mixture was then refluxed 1.5 hours, cooled and poured into a mixture comprised of 300 ml. of ice, 100 ml. of water and 225 ml. of concentrated hydrochloric acid. The organic phase was separated and the aqueous layer extracted with chloroform. The combined organic layers were washed with water, dried over magnesium sulfate, filtered and the solvent removed at reduced pressure to give an oil. Chromatography (2×) over alumina (ethyl acetate) followed by treatment with ether gave 3',4'-dimethoxydesoxybenzoin, m.p. 80°-81° C. The mixture was then refluxed 1.5 hours cooled poured into a mixture The organic phase was separated the aqueous layer extracted with chloroform The combined organic layers were washed with water dried over magnesium sulfate filtered the solvent removed at reduced pressure to give an oil

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

Procedure: The same procedure as that of Example 1 (1) to (8) was repeated except that 2-(3-pyridyl)ethyl chloride hydrochloride was replaced with 3,4-dimethoxyphenethyl chloride to prepare the intended compound. to prepare the intended compound