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A mixture of 3-(3,4-dimethyl-phenyl)-acrylic acid (19.269 g; 109.355 mmol) and 10percent palladium over activated charcoal (1.920 g) was placed under nitrogen before methanol (300 ml) was carefully added. The resulting suspension was placed under vacuum, then under hydrogen (1 atm), and the reaction mixture was vigorously stirred at rt for 4h. The reaction mixture was filtered over a pad of celite, and concentrated under reduced pressure to give the expected product 3- (3,4-dimethyl-phenyl)-propionic acid as a grey solid which was further dried under HV (19.070 g; 98percent). LC-MS: tR = 0.85 min; [M+H]+: no ionisation.
98%
With hydrogen In methanol at 20℃; for 4 h;
A mixture of 3-(3,4-dimethyl-phenyl)-acrylic acid (19.269 g; 109.355 mmol) and 10percent palladium over activated charcoal (1.920 g) was placed under nitrogen before MeOH (300 ml) was carefully added. The resulting suspension was placed under vacuum, then under hydrogen (1 atm), and the reaction mixture was vigorously stirred at rt for 4h. The reaction mixture was filtered over a pad of celite, and concentrated under reduced pressure to give the expected product 3-(3,4-dimethyl-phenyl)-propionic acid as a grey solid which was further dried under HV (19.070 g; 98percent). LC-MS: tR = 0.85 min; [M+H]+: no ionisation.
Reference：
[1] Journal of Heterocyclic Chemistry, 1987, vol. 24, # 3, p. 677 - 682
[2] Monatshefte fur Chemie, 1996, vol. 127, # 2, p. 185 - 200
[3] Patent: WO2008/26149, 2008, A1, . Location in patent: Page/Page column 22
[4] Patent: WO2008/78291, 2008, A1, . Location in patent: Page/Page column 39
[5] Collection of Czechoslovak Chemical Communications, 1967, vol. 32, p. 4082 - 4098
2
[ 102-46-5 ]
[ 105-53-3 ]
[ 25173-76-6 ]
Yield
Reaction Conditions
Operation in experiment
55%
With potassium hydroxide; sulfuric acid In diethyl ether; ethanol; water
Step 1) Synthesis of 3-(3,4-dimethylphenyl)propionic acid To a solution of 70.0 ml of diethyl malonate dissolved in 400 ml of dry ethanol was added 10.0 g of metallic sodium. The reaction mixture was stirred for 30 minutes and cooled to 0° C; and 66.5 g of 3,4-dimethylbenzyl chloride was added thereto. This reaction mixture was stirred at a room temperature for another 1 hour, heated at the boiling temperature for 4 hours and concentrated under a reduced pressure. The residue was dissolved in ethyl ether and the solution was washed with water. After further concentration under a reduced pressure, the organic phase was combined with 500 ml of water and 170 g of KOH; and this mixture was heated at the boiling temperature for 24 hours. The mixture was concentrated under a reduced pressure to about one half volume; then 200 ml of 98percent sulfuric acid was added slowly thereto. The resultant solution was heated at the boiling temperature for 24 hours, extracted twice with 300 ml of ethyl acetate. The organic solvent was distilled off under a reduced pressure and the residue was recrystallized from boiling hexane to obtain 42.1 g of the title compound as a white solid(yield: 55percent). m.p.: 82° C. 1 H-NMR(300 MHz, CDCl3) δ2.22(s, 3H, CH3), 2.24(s, 3H, CH3), 2.66(t, J=8 Hz, 2H, ArCH2), 2.89(t, J=8 Hz, 2H, CH2 CO), 6.93-7.70(m, 3H, ArH)
55%
With potassium hydroxide; sulfuric acid In diethyl ether; ethanol; water
Step 1) Synthesis of 3-(3,4-dimethylphenyl)propionic acid To a solution of 70.0ml of diethyl malonate dissolved in 400ml of dry ethanol was added 10.0g of metallic sodium. The reaction mixture was stirred for 30 minutes and cooled to 0°C; and 66.5g of 3,4-dimethylbenzyl chloride was added thereto. This reaction mixture was stirred at a room temperature for another 1 hour, heated at the boiling temperature for 4 hours and concentrated under a reduced pressure. The residue was dissolved in ethyl ether and the solution was washed with water. After further concentration under a reduced pressure, the organic phase was combined with 500ml of water and 170g of KOH; and this mixture was heated at the boiling temperature for 24 hours. The mixture was concentrated under a reduced pressure to about one half volume; then 200ml of 98percent sulfuric acid was added slowly thereto. The resultant solution was heated at the boiling temperature for 24 hours, extracted twice with 300ml of ethyl acetate. The organic solvent was distilled off under a reduced pressure and the residue was recrystallized from boiling hexane to obtain 42.lg of the title compound as a white solid(yield: 55percent). m.p.: 82°C 1H NMR(300MHz, CDCl3) δ 2.22(s, 3H, CH3), 2.24(s, 3H, CH3), 2.66(t, J=8Hz, 2H, ArCH2), 2.89(t, J=8Hz, 2H, CH2CO), 6.93-7.70(m, 3H, ArH)
With potassium hydroxide; sulfuric acid In diethyl ether; ethanol; water
PREPARATION EXAMPLE 1 Synthesis of 3-(3,4-dimethylphenyl)propylamine To a solution of 70.0 ml of diethyl malonate dissolved in 400 ml of dry ethanol was added 10.0 g of metalic sodium. The reaction mixture was stirred for 30 minutes and cooled to 0° C; and 66.5 g of 3,4-dimethylbenzyl chloride was added thereto. This reaction mixture was stirred for 1 hour at room temperature, heated at the boiling temperature for 4 hours and concentrated under reduced pressure to produce residues, which were dissolved in ethyl ether. This ethereal solution was washed with water. To the residues obtained after a further concentration of the organic phase were added 500 ml of water and 170 g of KOH; and this mixture was heated at the boiling temperature for 24 hours. This mixture was concentrated under reduced pressure until about a half of the amount remained, and 200 ml of sulfuric acid was then slowly added thereto. The resultant solution was heated at the boiling temperature for 24 hours, extracted twice with 300 ml of ethyl ether and evaporated under reduced pressure to obtain solids, which were recrystallized from boiling hexane to provide 42.1 g of 3-(3,4-dimethylphenyl)propanoic acid as a white solid (yield 55percent), having the characteristics of: m.p. 82° C.; NMR(CDCl3, 300 MHz) δ2.22(s, 3H, CH3), 2.24(s, 3H, CH3), 2.66(t, J=8 Hz, 2H, ArCH2), 2.89(t, J=8 Hz, 2H, CH2 CO), 6.93~7.70(m, 3H, ArH).
55%
With potassium hydroxide; sulfuric acid In diethyl ether; ethanol
Preparation Example 1: Synthesis of 3-(3,4-dimethylphenyl)propylamine To a solution of 70.0m of diethyl malonate dissolved in 400m of dry ethanol was added 10.0g of metalic sodium. The reaction mixture was stirred for 30 minutes and cooled to 0°C; and 66.5g of 3,4-dimethylbenzyl chloride was added thereto. This reaction mixture was stirred for 1 hour at room temperature, heated at the boiling temperature for 4 hours and concentrated under reduced pressure to produce residues, which were dissolved in ethyl ether. This ethereal solution was washed with water. To the residues obtained after a further concentration of the organic phase were added 500m of water and 170g of KOH; and this mixture was heated at the boiling temperature for 24 hours. This mixture was concentrated under reduced pressure until about a half of the amount remained, and 200m of sulfuric acid was then slowly added thereto. The resultant solution was heated at the boiling temperature for 24 hours, extracted twice with 300m of ethyl ether and evaporated under reduced pressure to obtain solids, which were recrystallized from boiling hexane to provide 42.1g of 3-(3,4-dimethylphenyl)propanoic acid as a white solid(yield 55percent), having the characteristics of: m.p. 82°C; NMR(CDCl3, 300MHz)δ 2.22(s, 3H, CH3), 2.24(s, 3H, CH3), 2.66(t, J=8Hz, 2H, ArCH2), 2.89(t, J=8Hz, 2H, CH2CO), 6.93~7.70(m, 3H, ArH).
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