3-(3,4-dimethoxyphenyl)prop-2-en-1-ol

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

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 0.42 g (2.0 mmol) of 3,4-dimethoxycinnamic acid in 50 ml MeOH was added SOCl2 (50 μl) and the mixture was stirred at 60° C. for 5 h. Methanol was taken to dryness and the obtained 3,4-dimethoxycinnamic acid methyl ester was reduced with 1M THF solution of diisobutylaluminum hydride (8.0 mmol) in absolute THF (50 ml) at 20° C. for 1 h. Water was added, the mixture was extracted with EtOAc, dried with MgSO4 and distilled in vacuo (Kugelrohr apparatus (Aldrich), 0.1 mm Hg, T. oven 185-190° C.) giving an off-white solid, yield 0.36 g (92%), m.p. 70-71° C. The product gave the following analytical data: the mixture was extracted with EtOAc dried with MgSO4 distilled in vacuo (Kugelrohr apparatus (Aldrich), 0.1 mm Hg, T. oven 185-190° C.) giving an off-white solid, yield 0.36 g (92%), m.p. 70-71° C The product gave the following analytical data

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

Procedure: Diethyl azodicarboxylate (26.1 g, 0.15 mol) and triphenyl phosphine (39.3 g, 0.15 mol) were added to a solution of 3-allyloxyphenol (15 g, 0.1 mol) and 3,4-dimethoxycinnamyl alcohol (19.4 g, 0.1 mol) in THF (100 ml). The mixture was stirred at room temperature overnight, and ethyl ether was added. The precipitate was filtered off, and the filtrate was evaporated to a residue, which was purified by HPLC using hexane-ethyl acetate (4:1 v/v) as a liquid phase. 3,4-Dimethoxycinnamyl allyloxyphenyl ether was isolated as a crystalline mass (7.4 g, 23%), m.p. 60°-60.5° C.; NMR (CDCl3): δ3.93, 3.94 (s, s, 2 OCH3), 4.57 (d, t, J=5.5, 1.5, 1.5 Hz, CH2CH=CH2), 4.71 (d, d, J=6.0, 1.5 Hz, CH=CHCH2), 5.28-5.50 (m, CH2CH=CH2), 6.10 (m, CH2CH=CH2 ), 6.26-6.40 (m, CH=CHCH2), 6.56-7.28 (m, ArH). The precipitate was filtered off the filtrate was evaporated to a residue, which was purified by HPLC

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

Procedure: Diethyl azodicarboxylate (26.1 g, 0.15 mol) and triphenyl phosphine (39.3 g, 0.15 mol) were added to a solution of 3-allyloxyphenol (15 g, 0.1 mol) and 3,4-dimethoxycinnamyl alcohol (19.4 g, 0.1 mol) in THF (100 ml). The mixture was stirred at room temperature overnight, and ethyl ether was added. The precipitate was filtered off, and the filtrate was evaporated to a residue, which was purified by HPLC using hexane-ethyl acetate (4:1 v/v) as a liquid phase. 3,4-Dimethoxycinnamyl allyloxyphenyl ether was isolated as a crystalline mass (7.4 g, 23%), m.p. 60°-60.5° C.; NMR (CDCl3): δ3.93, 3.94 (s, s, 2 OCH3), 4.57 (d, t, J=5.5, 1.5, 1.5 Hz, CH2CH=CH2), 4.71 (d, d, J=6.0, 1.5 Hz, CH=CHCH2), 5.28-5.50 (m, CH2CH=CH2), 6.10 (m, CH2CH=CH2 ), 6.26-6.40 (m, CH=CHCH2), 6.56-7.28 (m, ArH). The precipitate was filtered off the filtrate was evaporated to a residue, which was purified by HPLC

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

Procedure: A solution of lithium aluminum hydride (0.1 mol) in THF (100 ml) was added dropwise to a stirred suspension of 3,4-dimethoxycinnamic acid (41.6 g, 0.2 mol) in THF (150 ml) at room temperature. After the addition, the mixture was stirred for 2 hous, and the solution was evaporated in vacuo to a residue, which was partitioned between dichloromethane and aqueous sodium hydroxide. The organic layer was washed three times with water, dried, and evaporated to an oil. Crystallization from ethyl acetate-hexane gave 3,4-dimethoxycinnamyl alcohol (24 g, 62%), m.p. 76°-77° C. After the addition the solution was evaporated in vacuo to a residue, which was partitioned between dichloromethane and aqueous sodium hydroxide The organic layer was washed three times with water dried evaporated to an oil Crystallization from ethyl acetate-hexane

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

Procedure: A solution of lithium aluminum hydride (0.1 mol) in THF (100 ml) was added dropwise to a stirred suspension of 3,4-dimethoxycinnamic acid (41.6 g, 0.2 mol) in THF (150 ml) at room temperature. After the addition, the mixture was stirred for 2 hous, and the solution was evaporated in vacuo to a residue, which was partitioned between dichloromethane and aqueous sodium hydroxide. The organic layer was washed three times with water, dried, and evaporated to an oil. Crystallization from ethyl acetate-hexane gave 3,4-dimethoxycinnamyl alcohol (24 g, 62%), m.p. 76°-77° C. After the addition the solution was evaporated in vacuo to a residue, which was partitioned between dichloromethane and aqueous sodium hydroxide The organic layer was washed three times with water dried evaporated to an oil Crystallization from ethyl acetate-hexane

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

Procedure: A solution of lithium aluminum hydride (0.02 mol) in diethyl ether (20 ml) was added dropwise to a solution of ethyl 3,4-dimethoxycinnamate (9.4 g, 0.04 mol) in diethyl ether (150 ml), and the mixture was heated under reflux for 1 hour. Water (15 ml) and 2.5N sodium hydroxide (5 ml) were added to the cooled solution, and the precipitate was filtered off and washed with ether. The combined filtrates were washed with water, dried, and evaporated to dryness. The crude product was put on a column of silica gel and eluted with hexane-ethyl acetate (1.5:1, v/v). 3,4-Dimethoxycinnamyl alcohol was isolated as a crystalline mass (5.0 g, 65%), m.p. 76°-76.5° C. the mixture was heated under reflux for 1 hour the precipitate was filtered off washed with ether The combined filtrates were washed with water dried evaporated to dryness eluted with hexane-ethyl acetate (1.5:1

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

Procedure: A solution of lithium aluminum hydride (0.02 mol) in diethyl ether (20 ml) was added dropwise to a solution of ethyl 3,4-dimethoxycinnamate (9.4 g, 0.04 mol) in diethyl ether (150 ml), and the mixture was heated under reflux for 1 hour. Water (15 ml) and 2.5N sodium hydroxide (5 ml) were added to the cooled solution, and the precipitate was filtered off and washed with ether. The combined filtrates were washed with water, dried, and evaporated to dryness. The crude product was put on a column of silica gel and eluted with hexane-ethyl acetate (1.5:1, v/v). 3,4-Dimethoxycinnamyl alcohol was isolated as a crystalline mass (5.0 g, 65%), m.p. 76°-76.5° C. the mixture was heated under reflux for 1 hour the precipitate was filtered off washed with ether The combined filtrates were washed with water dried evaporated to dryness eluted with hexane-ethyl acetate (1.5:1

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

Procedure: To a solution of 3-(3,4-dimethoxyphenyl)prop-2-en-1-ol (270 mg) in dimethyl-sulfoxyde (4 mL) are added successively powdered potassium hydroxyde (175 mg 85% wt) and, portionwise, 1-(3-chloropropyl)piperidine, hydrochloride (250 mg). The mixture is stirred overnight at room temperature, then hydrolysed with water (80 mL). The solution is extracted twice with ethyl acetate (20 mL). The combined extracts are washed twice with water (10 mL), dried over magnesium sulphate, concentrated under reduced pressure and purified by chromatography over silica gel with a gradient dichloromethane/methanol from 98/2 to 90/10. Fractions containing the expected product are pooled, concentrated under reduced pressure, dissolved in 10 mL of dichloromethane, filtered over Millipore membrane and concentrated under reduced pressure. The base thus obtained is dissolved in 2 mL of ethanol and 100 μL of diethyl oxide. A solution of 88 mg of oxalic acid in 2 mL of ethanol is added. The precipitate that appears is filtered, washed with diethyl oxide and dried under reduced pressure at a temperature close to 40 C to give 185 mg of trans-1-{3-[3-(3,4-dimethoxyphenyl)allyloxy]propyl}piperidine, oxalate as a white powder melting at 111-112° C. The solution is extracted twice with ethyl acetate (20 mL) The combined extracts are washed twice with water (10 mL) dried over magnesium sulphate concentrated under reduced pressure purified by chromatography over silica gel with a gradient dichloromethane/methanol from 98/2 to 90/10 Fractions containing the expected product concentrated under reduced pressure dissolved in 10 mL of dichloromethane filtered over Millipore membrane concentrated under reduced pressure The base thus obtained The precipitate that appears is filtered washed with diethyl oxide dried under reduced pressure at a temperature close to 40 C

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

Procedure: To a solution of 3-(3,4-dimethoxyphenyl)prop-2-en-1-ol (270 mg) in dimethyl-sulfoxyde (4 mL) are added successively powdered potassium hydroxyde (175 mg 85% wt) and, portionwise, 1-(3-chloropropyl)piperidine, hydrochloride (250 mg). The mixture is stirred overnight at room temperature, then hydrolysed with water (80 mL). The solution is extracted twice with ethyl acetate (20 mL). The combined extracts are washed twice with water (10 mL), dried over magnesium sulphate, concentrated under reduced pressure and purified by chromatography over silica gel with a gradient dichloromethane/methanol from 98/2 to 90/10. Fractions containing the expected product are pooled, concentrated under reduced pressure, dissolved in 10 mL of dichloromethane, filtered over Millipore membrane and concentrated under reduced pressure. The base thus obtained is dissolved in 2 mL of ethanol and 100 μL of diethyl oxide. A solution of 88 mg of oxalic acid in 2 mL of ethanol is added. The precipitate that appears is filtered, washed with diethyl oxide and dried under reduced pressure at a temperature close to 40 C to give 185 mg of trans-1-{3-[3-(3,4-dimethoxyphenyl)allyloxy]propyl}piperidine, oxalate as a white powder melting at 111-112° C. The solution is extracted twice with ethyl acetate (20 mL) The combined extracts are washed twice with water (10 mL) dried over magnesium sulphate concentrated under reduced pressure purified by chromatography over silica gel with a gradient dichloromethane/methanol from 98/2 to 90/10 Fractions containing the expected product concentrated under reduced pressure dissolved in 10 mL of dichloromethane filtered over Millipore membrane concentrated under reduced pressure The base thus obtained The precipitate that appears is filtered washed with diethyl oxide dried under reduced pressure at a temperature close to 40 C

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 0.42 g (2.0 mmol) of 3,4-dimethoxycinnamic acid in 50 ml MeOH was added SOCl2 (50 μl) and the mixture was stirred at 60° C. for 5 h. Methanol was taken to dryness and the obtained 3,4-dimethoxycinnamic acid methyl ester was reduced with 1M THF solution of diisobutylaluminum hydride (8.0 mmol) in absolute THF (50 ml) at 20° C. for 1 h. Water was added, the mixture was extracted with EtOAc, dried with MgSO4 and distilled in vacuo (Kugelrohr apparatus (Aldrich), 0.1 mm Hg, T. oven 185-190° C.) giving an off-white solid, yield 0.36 g (92%), m.p. 70-71° C. The product gave the following analytical data: the mixture was extracted with EtOAc dried with MgSO4 distilled in vacuo (Kugelrohr apparatus (Aldrich), 0.1 mm Hg, T. oven 185-190° C.) giving an off-white solid, yield 0.36 g (92%), m.p. 70-71° C The product gave the following analytical data

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

Procedure: Diethyl azodicarboxylate (26.1 g, 0.15 mol) and triphenyl phosphine (39.3 g, 0.15 mol) were added to a solution of 3-allyloxyphenol (15 g, 0.1 mol) and 3,4-dimethoxycinnamyl alcohol (19.4 g, 0.1 mol) in THF (100 ml). The mixture was stirred at room temperature overnight, and ethyl ether was added. The precipitate was filtered off, and the filtrate was evaporated to a residue, which was purified by HPLC using hexane-ethyl acetate (4:1 v/v) as a liquid phase. 3,4-Dimethoxycinnamyl allyloxyphenyl ether was isolated as a crystalline mass (7.4 g, 23%), m.p. 60°-60.5° C.; NMR (CDCl3): δ3.93, 3.94 (s, s, 2 OCH3), 4.57 (d, t, J=5.5, 1.5, 1.5 Hz, CH2CH=CH2), 4.71 (d, d, J=6.0, 1.5 Hz, CH=CHCH2), 5.28-5.50 (m, CH2CH=CH2), 6.10 (m, CH2CH=CH2 ), 6.26-6.40 (m, CH=CHCH2), 6.56-7.28 (m, ArH). The precipitate was filtered off the filtrate was evaporated to a residue, which was purified by HPLC