2-methoxy-1-phenylethanone

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

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

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

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-t-Butoxycarbonylaminopyrrolidine (560 mg) was dissolved in methanol (5 ml), the solution was added with acetic acid (170 μl), 2-methoxyacetophenone (140 μl) and sodium cyanoborohydride (45 mg), and the mixture was stirred at 50° C. for 20 hours. The reaction mixture was added with 5 N hydrochloric acid (10 ml), the mixture was stirred at room temperature for 2 hours, and then made basic with potassium carbonate, and methanol was evaporated under reduced pressure. The reaction mixture was added with chloroform, the layers were separated, the organic layer was dried over anhydrous magnesium sulfate and filtered, and then the filtrate was concentrated under reduced pressure to obtain the title compound (83 mg). the mixture was stirred at room temperature for 2 hours was evaporated under reduced pressure The reaction mixture was added with chloroform the layers were separated the organic layer was dried over anhydrous magnesium sulfate filtered the filtrate was concentrated under reduced pressure

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

Procedure: To a solution of 54 mg of 4-[(S)-3-aminopyrrolidin-1-yl]-N,N-dimethyl-benzenesulfonamide and 30 mg of 2-methoxyacetophenone in 1 ml of THF was added 85 mg of titanium isopropoxide, and the mixture was stirred at room temperature for 1 day. Further, 12 mg of sodium borohydride was added to the reaction mixture, and then, 0.3 ml of methanol was added to the mixture, and the mixture was stirred at room temperature for 4 hours. To the reaction mixture was added 0.5 ml of 28% aqueous ammonia solution, the mixture was stirred, and then, insoluble materials were removed and the solvent was evaporated. The residue was purified by LC/MS to obtain 61 mg of 4-[(S)-3-[1-(2-methoxyphenyl)ethylamino]pyrrolidin-1-yl]-N,N-dimethyl-benzenesulfonamide. The 4-[(S)-3-[1-(2-methoxyphenyl)ethylamino]pyrrolidin-1-yl]-N,N-dimethyl-benzenesulfonamide was dissolved by adding 1 ml of tert-butanol, 0.15 ml of 2M aqueous hydrochloric acid was added thereto, and after stirring the mixture, it was freeze-dried to obtain 4-[(S)-3-[1-(2-methoxyphenyl)ethylamino]pyrrolidin-1-yl]-N,N-dimethyl-benzenesulfonamide dihydrochloride (the following Table Y, Example 13.001). the mixture was stirred at room temperature for 4 hours the mixture was stirred insoluble materials were removed the solvent was evaporated The residue was purified by LC/MS

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

Procedure: 2-Methoxy-1-phenyl-ethanone (5.00 g) dissolved in tetrahydrofuran (50 mL) was added to 2 M allylmagnesium chloride in tetrahydrofuran (21 mL) at room temperature. The solution was stirred at room temperature for 3 h and then 10% aqueous NH4Cl solution (50 mL) was added. The resulting mixture was extracted with tert-butyl methyl ether (3×50 mL) and the combined extracts were washed with water (50 mL) and brine (50 mL). The solvent was evaporated to afford the title compound as a colorless oil. The resulting mixture was extracted with tert-butyl methyl ether (3×50 mL) the combined extracts were washed with water (50 mL) and brine (50 mL) The solvent was evaporated

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

Procedure: 1-Chloro-2-methoxymethoxybenzene (20.0 g) was combined with 72.5 ml of 1.6 M n-butyl lithium in hexane at 0° C. with stirring and allowed to react for 4 hours. A solution of 16.0 ml of 2-methoxyacetophenone in 20 ml of tetrahydrofuran was then added with stirring. After a short reaction period, water and ether were added and the ether layer was dried over magnesium sulfate, filtered, and concentrated by evaporation under reduced pressure to obtain an oil. This was purified by liquid chromatography, eluting with a 95:5 mixture of hexane and ethyl acetate, to obtain 6.67 g of the title compound as an oil. The assigned structure was consistent with the proton NMR spectrum. to react for 4 hours with stirring were added the ether layer was dried over magnesium sulfate filtered concentrated by evaporation under reduced pressure to obtain an oil This was purified by liquid chromatography eluting with a 95:5 mixture of hexane and ethyl acetate

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

Procedure: 2-Methoxy-1-phenyl-ethanone (5.00 g) dissolved in tetrahydrofuran (50 mL) was added to 2 M allylmagnesium chloride in tetrahydrofuran (21 mL) at room temperature. The solution was stirred at room temperature for 3 h and then 10% aqueous NH4Cl solution (50 mL) was added. The resulting mixture was extracted with tert-butyl methyl ether (3×50 mL) and the combined extracts were washed with water (50 mL) and brine (50 mL). The solvent was evaporated to afford the title compound as a colorless oil. The resulting mixture was extracted with tert-butyl methyl ether (3×50 mL) the combined extracts were washed with water (50 mL) and brine (50 mL) The solvent was evaporated

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

Procedure: 2-Methoxy-1-phenyl-ethanone (5.00 g) dissolved in tetrahydrofuran (50 mL) was added to 2 M allylmagnesium chloride in tetrahydrofuran (21 mL) at room temperature. The solution was stirred at room temperature for 3 h and then 10% aqueous NH4Cl solution (50 mL) was added. The resulting mixture was extracted with tert-butyl methyl ether (3×50 mL) and the combined extracts were washed with water (50 mL) and brine (50 mL). The solvent was evaporated to afford the title compound as a colorless oil. The resulting mixture was extracted with tert-butyl methyl ether (3×50 mL) the combined extracts were washed with water (50 mL) and brine (50 mL) The solvent was evaporated

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

Procedure: The procedure is as in Example 4 for the preparation of ethyl 6-phenyl-6-oxo-5-methylthio-2-dimethylamino-2,4-hexadienoate, starting with N-(3-dimethylamino-3-ethoxycarbonylpropenylidene)-N-methylmethanaminium tetrafluoroborate (11.4 g), a 2M ethanolic solution of sodium ethylate (20 cc) and α-methoxyacetophenone (6 g) in ethanol (50 cc). After purification by chromatography on a silica column with a mixture of dicholoromethane and ethyl acetate (50:50 by volume) as eluent, ethyl 2-dimethylamino-5-methoxy-6-oxo-6-phenyl-2,4-hexadienoate (8.1 g) is obtained, and is used in the crude state in the subsequent syntheses. After purification by chromatography on a silica column with a mixture of dicholoromethane and ethyl acetate (50:50 by volume) as eluent

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

Procedure: The procedure is as in Example 4 for the preparation of ethyl 6-phenyl-6-oxo-5-methylthio-2-dimethylamino-2,4-hexadienoate, starting with N-(3-dimethylamino-3-ethoxycarbonylpropenylidene)-N-methylmethanaminium tetrafluoroborate (11.4 g), a 2M ethanolic solution of sodium ethylate (20 cc) and α-methoxyacetophenone (6 g) in ethanol (50 cc). After purification by chromatography on a silica column with a mixture of dicholoromethane and ethyl acetate (50:50 by volume) as eluent, ethyl 2-dimethylamino-5-methoxy-6-oxo-6-phenyl-2,4-hexadienoate (8.1 g) is obtained, and is used in the crude state in the subsequent syntheses. After purification by chromatography on a silica column with a mixture of dicholoromethane and ethyl acetate (50:50 by volume) as eluent

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

Procedure: 2-Methoxy-1-phenyl-ethanone (5.00 g) dissolved in tetrahydrofuran (50 mL) was added to 2 M allylmagnesium chloride in tetrahydrofuran (21 mL) at room temperature. The solution was stirred at room temperature for 3 h and then 10% aqueous NH4Cl solution (50 mL) was added. The resulting mixture was extracted with tert-butyl methyl ether (3×50 mL) and the combined extracts were washed with water (50 mL) and brine (50 mL). The solvent was evaporated to afford the title compound as a colorless oil. Yield: 6.40 g (quantitative). Mass spectrum (ESI+): m/z=175 [M+H−H2O]+ The resulting mixture was extracted with tert-butyl methyl ether (3×50 mL) the combined extracts were washed with water (50 mL) and brine (50 mL) The solvent was evaporated