3-(3,4-Dimethoxyphenyl)propanamide

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

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

Procedure: 3-(3,4-dimethoxyphenyl)propionic acid amide (20.5 mg, 0.1 mmol) prepared in the same manner as in Reference Synthetic Example 8 was dissolved in tetrahydrofuran (2 ml) in nitrogen atmosphere, and under cooling with ice, tetrakistriphenylphosphine palladium(0) (5 mg, 0.004 mmol) was added, and then a tetrahydrofuran solution (0.5 ml) of tri-n-butyltin hydride (35 μl, 0.13 mmol) was dropwise added. After stirring for 30 minutes, the solution was concentrated under reduced pressure, and the residue was purified by tin-layer silica gel column chromatography (hexane:ethyl acetate=1:1) to give (E)-2-(tributylstannyl)-3-(3,4-dimethoxyphenyl)acrylamide (14.8 mg, 30%) as a pale yellow oily substance. was added the solution was concentrated under reduced pressure the residue was purified by tin-layer silica gel column chromatography (hexane:ethyl acetate=1:1)

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

Procedure: 3-(3,4-dimethoxyphenyl)propionic acid amide (20.5 mg, 0.1 mmol) prepared in the same manner as in Reference Synthetic Example 8 was dissolved in tetrahydrofuran (2 ml) in nitrogen atmosphere, and under cooling with ice, tetrakistriphenylphosphine palladium(0) (5 mg, 0.004 mmol) was added, and then a tetrahydrofuran solution (0.5 ml) of tri-n-butyltin hydride (35 μl, 0.13 mmol) was dropwise added. After stirring for 30 minutes, the solution was concentrated under reduced pressure, and the residue was purified by tin-layer silica gel column chromatography (hexane:ethyl acetate=1:1) to give (E)-2-(tributylstannyl)-3-(3,4-dimethoxyphenyl)acrylamide (14.8 mg, 30%) as a pale yellow oily substance. was added the solution was concentrated under reduced pressure the residue was purified by tin-layer silica gel column chromatography (hexane:ethyl acetate=1:1)

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

Procedure: To a 25 ml eggplant-shaped bottle were added 0.15 g (0.717 mmol) 3-(3,4-dimethoxy-phenyl)-propanamide prepared in step 2, 0.16 g (0.717 mmol) P2S5 and 10 ml THF. A reflux condensing tube carrying a calcium chloride drying tube was mounted. The mixture was refluxed for 1 hour under magnetic agitation, concentrated under a reduced pressure, partitioned between ethyl acetate and saturated NaHCO3 solution each of 15 ml. The aqueous layer was extracted with ethyl acetate twice ×10 ml. The organic phase was combined, washed with saturated brine twice ×15 ml, dried over Na2SO4, filtered and concentrated to obtain a solid crude product which was purified under a reduced pressure by silica gel column chromatography eluted with petroleum ether and ethyl acetate at a ratio of 10:1 (V:V) to obtain a 0.11 g product as a white solid in a yield of 68.8%, mp: 140-141 └. 1H-NMR (CDCl3, 600 MHz) δ: 2.93 (2H, t, J=7.20 Hz, CH2), 3.07 (2H, t, J=7.84 Hz, CH2), 3.86 (3H, s, CH3O), 3.87 (3H, s, CH3O), 6.62 (1H, br), 6.75˜6.82 (3H, m, ArH), 7.35 (1H, br); ESI-MS (m/e, %): 248.3 (M+Na, 100), 226.3 (M+H, 64). A reflux condensing tube The mixture was refluxed for 1 hour under magnetic agitation concentrated under a reduced pressure partitioned between ethyl acetate and saturated NaHCO3 solution each of 15 ml The aqueous layer was extracted with ethyl acetate twice ×10 ml washed with saturated brine twice ×15 ml dried over Na2SO4 filtered concentrated to obtain a solid crude product which was purified under a reduced pressure by silica gel column chromatography eluted with petroleum ether and ethyl acetate at a ratio of 10:1 (V:V)

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

Procedure: To a 25 ml eggplant-shaped bottle were added 0.15 g (0.717 mmol) 3-(3,4-dimethoxy-phenyl)-propanamide prepared in step 2, 0.16 g (0.717 mmol) P2S5 and 10 ml THF. A reflux condensing tube carrying a calcium chloride drying tube was mounted. The mixture was refluxed for 1 hour under magnetic agitation, concentrated under a reduced pressure, partitioned between ethyl acetate and saturated NaHCO3 solution each of 15 ml. The aqueous layer was extracted with ethyl acetate twice ×10 ml. The organic phase was combined, washed with saturated brine twice ×15 ml, dried over Na2SO4, filtered and concentrated to obtain a solid crude product which was purified under a reduced pressure by silica gel column chromatography eluted with petroleum ether and ethyl acetate at a ratio of 10:1 (V:V) to obtain a 0.11 g product as a white solid in a yield of 68.8%, mp: 140-141 └. 1H-NMR (CDCl3, 600 MHz) δ: 2.93 (2H, t, J=7.20 Hz, CH2), 3.07 (2H, t, J=7.84 Hz, CH2), 3.86 (3H, s, CH3O), 3.87 (3H, s, CH3O), 6.62 (1H, br), 6.75˜6.82 (3H, m, ArH), 7.35 (1H, br); ESI-MS (m/e, %): 248.3 (M+Na, 100), 226.3 (M+H, 64). A reflux condensing tube The mixture was refluxed for 1 hour under magnetic agitation concentrated under a reduced pressure partitioned between ethyl acetate and saturated NaHCO3 solution each of 15 ml The aqueous layer was extracted with ethyl acetate twice ×10 ml washed with saturated brine twice ×15 ml dried over Na2SO4 filtered concentrated to obtain a solid crude product which was purified under a reduced pressure by silica gel column chromatography eluted with petroleum ether and ethyl acetate at a ratio of 10:1 (V:V)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3-(3,4-dimethoxy-phenyl)--propionamide (11.09 g, 53.00 mmol) in anhydrous THF (400 ml) was slowly added to a stirred, ice-cooled suspension of LiAlH4 (4.02 g, 106.00 mmol) in anhydrous THF (170 ml). Upon completion of the addition, the mixture was stirred at reflux for 2 h. After cooling to 0° C., H2O (5 ml) and NaOH 1N (5 ml) were added dropwise to decompose the excess of hydride. The suspension was then filtered and the residue after evaporation was partitioned between H2O (40 ml) and CH2Cl2 (100 ml). The organic layer was washed with saturated aqueous NaHCO3 and brine, dried over anhydrous MgSO4, and concentrated under reduced pressure to give the crude amine (7.00 g, 35.84 mmol, 68%) as a yellow oil. cooled Upon completion of the addition at reflux for 2 h The suspension was then filtered the residue after evaporation was partitioned between H2O (40 ml) and CH2Cl2 (100 ml) The organic layer was washed with saturated aqueous NaHCO3 and brine dried over anhydrous MgSO4 concentrated under reduced pressure

Conditions: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 3-(3,4-dimethoxy-phenyl)-propionic acid (10.0 g, 47.56 mmol) in dry THF (175 ml), under nitrogen, was added TEA (7.3 ml, 52.44 mmol), and the resulting mixture was cooled to −10° C. before ethyl chloroformate (5 ml, 52.47 mmol) was added dropwise. After stirring at −10° C. (20 min), ammonium hydroxide (25% in water, 105 ml) in THF (105 ml) was added and the mixture was stirred at −15° C. for 30 min and then at RT for 1.5 h. The reaction mixture was concentrated in vacuo, extracted three times with CH2Cl2 and the combined organic extracts were washed with saturated aqueous NaHCO3 and brine. The organic phase was dried over anhydrous MgSO4, filtered and concentrated to give the title compound (9.73 g, 46.50 mmol, 97%) as a colorless solid. No further purification of the crude amide was necessary. was added dropwise was added at RT for 1.5 h The reaction mixture was concentrated in vacuo extracted three times with CH2Cl2 the combined organic extracts were washed with saturated aqueous NaHCO3 and brine The organic phase was dried over anhydrous MgSO4 filtered concentrated

Conditions: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 3-(3,4-dimethoxy-phenyl)-propionic acid (10.0 g, 47.56 mmol) in dry THF (175 ml), under nitrogen, was added TEA (7.3 ml, 52.44 mmol), and the resulting mixture was cooled to −10° C. before ethyl chloroformate (5 ml, 52.47 mmol) was added dropwise. After stirring at −10° C. (20 min), ammonium hydroxide (25% in water, 105 ml) in THF (105 ml) was added and the mixture was stirred at −15° C. for 30 min and then at RT for 1.5 h. The reaction mixture was concentrated in vacuo, extracted three times with CH2Cl2 and the combined organic extracts were washed with saturated aqueous NaHCO3 and brine. The organic phase was dried over anhydrous MgSO4, filtered and concentrated to give the title compound (9.73 g, 46.50 mmol, 97%) as a colorless solid. No further purification of the crude amide was necessary. was added dropwise was added at RT for 1.5 h The reaction mixture was concentrated in vacuo extracted three times with CH2Cl2 the combined organic extracts were washed with saturated aqueous NaHCO3 and brine The organic phase was dried over anhydrous MgSO4 filtered concentrated

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3-(3,4-dimethoxy-phenyl)-propionamide (11.1 g, 53.0 mmol) in anhydrous THF (400 ml) is slowly added to a stirred, ice-cooled suspension of LiAlH4 (4.02 g, 106 mmol) in anhydrous THF (170 mL). Upon completion of the addition, the mixture is stirred at reflux for 2 h. After cooling to 0° C., H2O (5 mL) and NaOH 1N (5 mL) are added dropwise to decompose the excess of hydride. The suspension is filtered and evaporated. The residue is partitioned between H2O (40 mL) and CH2Cl2 (100 mL). The organic layer is washed with saturated aqueous NaHCO3 and brine, dried over anhydrous MgSO4, and concentrated under reduced pressure to give the title compound as a yellow oil. cooled Upon completion of the addition at reflux for 2 h The suspension is filtered evaporated The residue is partitioned between H2O (40 mL) and CH2Cl2 (100 mL) The organic layer is washed with saturated aqueous NaHCO3 and brine dried over anhydrous MgSO4 concentrated under reduced pressure

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3-(3,4-dimethoxy-phenyl)-propionamide (11.1 g, 53.0 mmol) in anhydrous THF (400 ml) is slowly added to a stirred, ice-cooled suspension of LiAlH4 (4.02 g, 106 mmol) in anhydrous THF (170 mL). Upon completion of the addition, the mixture is stirred at reflux for 2 h. After cooling to 0° C., H2O (5 mL) and NaOH 1N (5 mL) are added dropwise to decompose the excess of hydride. The suspension is filtered and evaporated. The residue is partitioned between H2O (40 mL) and CH2Cl2 (100 mL). The organic layer is washed with saturated aqueous NaHCO3 and brine, dried over anhydrous MgSO4, and concentrated under reduced pressure to give the title compound as a yellow oil. cooled Upon completion of the addition at reflux for 2 h The suspension is filtered evaporated The residue is partitioned between H2O (40 mL) and CH2Cl2 (100 mL) The organic layer is washed with saturated aqueous NaHCO3 and brine dried over anhydrous MgSO4 concentrated under reduced pressure

Conditions: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 3-(3,4-dimethoxy-phenyl)-propionic acid (10.0 g, 47.6 mmol) in dry THF (175 mL), under nitrogen, is added TEA (7.3 ml, 52.4 mmol). The resulting mixture is cooled to −10° C. before ethyl chloroformate (5.0 ml, 52 mmol) is added dropwise. After stirring at −10° C. (20 min), ammonium hydroxide (25% in water, 105 ml) in THF (105 mL) is added and the mixture is stirred at −15° C. for 30 min and then at rt for 1.5 h. The reaction mixture is concentrated in vacuo, extracted three times with CH2Cl2 and the combined organic extracts are washed with saturated aqueous NaHCO3 and brine. The organic phase is dried over anhydrous MgSO4, filtered and concentrated to give the title compound as a colorless solid. is added dropwise is added at rt for 1.5 h The reaction mixture is concentrated in vacuo extracted three times with CH2Cl2 the combined organic extracts are washed with saturated aqueous NaHCO3 and brine The organic phase is dried over anhydrous MgSO4 filtered concentrated

Conditions: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 3-(3,4-dimethoxy-phenyl)-propionic acid (10.0 g, 47.6 mmol) in dry THF (175 mL), under nitrogen, is added TEA (7.3 ml, 52.4 mmol). The resulting mixture is cooled to −10° C. before ethyl chloroformate (5.0 ml, 52 mmol) is added dropwise. After stirring at −10° C. (20 min), ammonium hydroxide (25% in water, 105 ml) in THF (105 mL) is added and the mixture is stirred at −15° C. for 30 min and then at rt for 1.5 h. The reaction mixture is concentrated in vacuo, extracted three times with CH2Cl2 and the combined organic extracts are washed with saturated aqueous NaHCO3 and brine. The organic phase is dried over anhydrous MgSO4, filtered and concentrated to give the title compound as a colorless solid. is added dropwise is added at rt for 1.5 h The reaction mixture is concentrated in vacuo extracted three times with CH2Cl2 the combined organic extracts are washed with saturated aqueous NaHCO3 and brine The organic phase is dried over anhydrous MgSO4 filtered concentrated