methyl 2-phenylpropanoate

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

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: DBU (2.03 g, 13.3 mmol) was added to a mixture of 2-phenylpropionic acid (2.0 g, 13.3 mmol) in DMC (20 mL) and the resulting mixture was heated to reflux (90° C.) for 5 hours. The reaction mixture was cooled to ambient temperature and diluted with CH2Cl2 (50 mL) and water (40 mL). The organic layer was separated and washed in sequence with 2 M HCl (2×40 mL), saturated aqueous NaHCO3 (40 mL) and water (2×50 mL). The organic layer was dried over Na2SO4, filtered and concentrated under vacuum to give methyl 2-phenylpropionate as an oil. the resulting mixture was heated The reaction mixture was cooled to ambient temperature The organic layer was separated washed in sequence with 2 M HCl (2×40 mL), saturated aqueous NaHCO3 (40 mL) and water (2×50 mL) The organic layer was dried over Na2SO4 filtered concentrated under vacuum

Conditions: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of n-butyl lithium in hexane (1.44N, 60.0 ml, 86.4 mmol) was added to a solution of diisopropylamine (9.07 g, 89.6 mmol) in anhydrous THF (200 ml) cooled at -30° C. under argon atmosphere, and the mixture was stirred for 20 minutes. To this reaction mixture were added a solution of methyl 2-phenylpropionate (10.5 g, 64.0 mmol) in 10 ml of anhydrous THF and HMPA (16.5 g, 92.0 mmol), and the mixture was stirred at -30° C. for 10 minutes and then at 0° C. for 45 minutes. To this reaction solution was added a solution of methyl iodide (13.6 g, 96.0 mmol) in anhydrous THF (30 ml) at -30° C., and the mixture was stirred at -30° C. for 1 hour. This reaction mixture was added to an aqueous saturated solution of ammonium chloride (400 ml) and water (50 ml) was added. The mixture was extracted with ether (400 ml). The aqueous layer further extracted with ethyl acetate. The combined organic layers were washed with water (300 ml) and brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was distilled (b.p. 99°-100° C./6 mmHg) to give an oil of methyl 2-methyl-2-phenylpropionate (7.63 g, 42.9 mmol, 67.0%). This compound was assigned the structure by the following data: the mixture was stirred at -30° C. for 10 minutes at 0° C. for 45 minutes the mixture was stirred at -30° C. for 1 hour was added The mixture was extracted with ether (400 ml) The aqueous layer further extracted with ethyl acetate The combined organic layers were washed with water (300 ml) and brine dried over anhydrous magnesium sulfate concentrated The residue was distilled (b.p. 99°-100° C./6 mmHg)

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of n-butyl lithium in hexane (1.44N, 75 ml, 108 mmol) was added to a solution of diisopropylamine (11.3 g, 112 mmol) in anhydrous THF (200 ml) cooled at -20° C. under argon atmosphere, and the mixture was stirred for 30 minutes. The reaction mixture was cooled to -78° C. To this solution were added a solution of methyl phenylacetate (12.0 g, 80.0 mmol) in 15 ml of anhydrous THF and HMPA (20.6 g, 115 mmol). The mixture was stirred at -78° C. for 1 hour and then at -30° C. for 30 minutes. To this reaction solution was added a solution of methyl iodide (17.0 g, 120 mmol) in anhydrous THF (30 ml) at -78° C., and the mixture was stirred at -78° C. for 1.5 hours. The reaction mixture was allowed to warm to room temperature and diluted with an aqueous saturated solution of ammonium chloride (300 ml) and water (150 ml). The mixture was extracted with ether (400 ml). The aqueous layer was further extracted with ether (200 ml×2). The combined organic layers were washed with water (200 ml) and brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was distilled (b.p. 92°-93° C./10 mmHg) to give an oil of methyl 2-phenylpropionate (11.3 g, 68.9 mmol, 86.1%). This compound was assigned to the structure by the following data: The reaction mixture was cooled to -78° C The mixture was stirred at -78° C. for 1 hour at -30° C. for 30 minutes the mixture was stirred at -78° C. for 1.5 hours to warm to room temperature The mixture was extracted with ether (400 ml) The aqueous layer was further extracted with ether (200 ml×2) The combined organic layers were washed with water (200 ml) and brine dried over anhydrous magnesium sulfate concentrated The residue was distilled (b.p. 92°-93° C./10 mmHg)

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of n-butyl lithium in hexane (1.44N, 75 ml, 108 mmol) was added to a solution of diisopropylamine (11.3 g, 112 mmol) in anhydrous THF (200 ml) cooled at -20° C. under argon atmosphere, and the mixture was stirred for 30 minutes. The reaction mixture was cooled to -78° C. To this solution were added a solution of methyl phenylacetate (12.0 g, 80.0 mmol) in 15 ml of anhydrous THF and HMPA (20.6 g, 115 mmol). The mixture was stirred at -78° C. for 1 hour and then at -30° C. for 30 minutes. To this reaction solution was added a solution of methyl iodide (17.0 g, 120 mmol) in anhydrous THF (30 ml) at -78° C., and the mixture was stirred at -78° C. for 1.5 hours. The reaction mixture was allowed to warm to room temperature and diluted with an aqueous saturated solution of ammonium chloride (300 ml) and water (150 ml). The mixture was extracted with ether (400 ml). The aqueous layer was further extracted with ether (200 ml×2). The combined organic layers were washed with water (200 ml) and brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was distilled (b.p. 92°-93° C./10 mmHg) to give an oil of methyl 2-phenylpropionate (11.3 g, 68.9 mmol, 86.1%). This compound was assigned to the structure by the following data: The reaction mixture was cooled to -78° C The mixture was stirred at -78° C. for 1 hour at -30° C. for 30 minutes the mixture was stirred at -78° C. for 1.5 hours to warm to room temperature The mixture was extracted with ether (400 ml) The aqueous layer was further extracted with ether (200 ml×2) The combined organic layers were washed with water (200 ml) and brine dried over anhydrous magnesium sulfate concentrated The residue was distilled (b.p. 92°-93° C./10 mmHg)

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

Procedure: Into the cathode chamber of an electrolytic cell divided with an ion-exchange resin diaphragm was placed a solution of 10 mmols of methyl phenylacetate, 12 mmols of methyl methanesulfonate and 1.0 g of tetraethylammonium tosylate in 30 ml of anhydrous dimethylformamide. And the anode chamber of the electrolytic cell was supplied with a solution of 3.0 g of tetraethylammonium tosylate in 10 ml of anhydrous dimethylformamide. Constant current electrolysis was conducted at 0.2 A/cm2 with use of platinum for both the anode and cathode. After passing 1.5 F of electricity per mol of the methyl phenylacetate through the solution at room temperature, the cathode solution was added to a saturated aqueous solution of ammonium chloride and the mixture was extracted twice with ether. The ether was removed by distillation and the residue was purified by silica gel column chromatography using hexane-ethyl acetate (10:1), giving methyl α-methylphenylacetate in a yield of 78% and α-methylphenylacetic acid in a yield of 15%. The spectral data of the ester were as follows. at room temperature the mixture was extracted twice with ether The ether was removed by distillation the residue was purified by silica gel column chromatography

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

Procedure: 2-Phenylpropionic acid (8.4 g, 56 mmol) in methanol (180 ml) and concentrated H2SO4 (2 ml) were heated at reflux for 4 hours. The reaction was cooled down to room temperature and concentrated in vacuo (~30 ml), which was poured into ice water (~100 ml). The products were extracted with Et2O (150 ml×3), which was washed with saturated NaHCO3, H2O and dried over MgSO4. Filtration and evaporation of solvent yielded a yellow oil (8.9 g), which was distilled to give a colorless oil (8.34 g, 51 mmol, 91%, b.p. 73° C./1.5 mm Hg). at reflux for 4 hours concentrated in vacuo (~30 ml), which was poured into ice water (~100 ml) The products were extracted with Et2O (150 ml×3), which was washed with saturated NaHCO3, H2O dried over MgSO4 Filtration and evaporation of solvent

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

Procedure: 2-Phenylpropionic acid (8.4 g, 56 mmol) in methanol (180 ml) and concentrated H2SO4 (2 ml) were heated at reflux for 4 hours. The reaction was cooled down to room temperature and concentrated in vacuo (~30 ml), which was poured into ice water (~100 ml). The products were extracted with Et2O (150 ml×3), which was washed with saturated NaHCO3, H2O and dried over MgSO4. Filtration and evaporation of solvent yielded a yellow oil (8.9 g), which was distilled to give a colorless oil (8.34 g, 51 mmol, 91%, b.p. 73° C./1.5 mm Hg). at reflux for 4 hours concentrated in vacuo (~30 ml), which was poured into ice water (~100 ml) The products were extracted with Et2O (150 ml×3), which was washed with saturated NaHCO3, H2O dried over MgSO4 Filtration and evaporation of solvent

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

Procedure: A solution of lithium bis(trimethylsilyl)amide (1M in tetrahydrofuran, 3.04 mL, 3.04 mmol, 1 equiv) under a N2 atmosphere was cooled to 0° C. and treated with a solution of methyl 2-phenylpropionate (0.500 g, 3.04 mmol, 1 equiv) in dry tetrahydrofuran (2 mL). The reaction was stirred at 0° C. for 2 hrs, then cooled to −78° C. and treated with hexamethylphosphoric triamide (0.4 mL) and bromomethylcyclopentane (0.745 g, 4.568 mmol, 1.5 equiv). Stirred the reaction at −78° C. and allowed the bath to slowly warm to room temperature overnight. After 15 hrs, the reaction mixture was quenched with 10% aq NH4Cl (50 mL) and extracted with ethyl acetate (100 mL). The organic extract was washed with H2O (50 mL) and brine, then dried over Na2SO4, filtered, and concentrated by rotary evaporation. The residue was purified by SiO2 flash chromatography with 2:3 dichloromethane/hexanes to give the product as colorless oil (1.38 g, 5.60 mmol, 92%). 1H NMR (300 MHz, DMSO-d6): δ ppm 0.90-1.12 (m, 2H) 1.32-1.72 (m, 10H) 1.97-2.12 (m, 2H) 3.58 (s, 3H) 7.19-7.35 (m, 5H); MS (APCI+) m/z 247 (M+H)+. cooled to −78° C. Stirred the reaction at −78° C. to slowly warm to room temperature overnight After 15 hrs the reaction mixture was quenched with 10% aq NH4Cl (50 mL) extracted with ethyl acetate (100 mL) The organic extract was washed with H2O (50 mL) and brine dried over Na2SO4 filtered concentrated by rotary evaporation The residue was purified by SiO2 flash chromatography with 2:3 dichloromethane/hexanes

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

Procedure: A solution of lithium bis(trimethylsilyl)amide (1M in tetrahydrofuran, 3.04 mL, 3.04 mmol, 1 equiv) under a N2 atmosphere was cooled to 0° C. and treated with a solution of methyl 2-phenylpropionate (0.500 g, 3.04 mmol, 1 equiv) in dry tetrahydrofuran (2 mL). The reaction was stirred at 0° C. for 2 hrs, then cooled to −78° C. and treated with hexamethylphosphoric triamide (0.4 mL) and bromomethylcyclopentane (0.745 g, 4.568 mmol, 1.5 equiv). Stirred the reaction at −78° C. and allowed the bath to slowly warm to room temperature overnight. After 15 hrs, the reaction mixture was quenched with 10% aq NH4Cl (50 mL) and extracted with ethyl acetate (100 mL). The organic extract was washed with H2O (50 mL) and brine, then dried over Na2SO4, filtered, and concentrated by rotary evaporation. The residue was purified by SiO2 flash chromatography with 2:3 dichloromethane/hexanes to give the product as colorless oil (1.38 g, 5.60 mmol, 92%). 1H NMR (300 MHz, DMSO-d6): δ ppm 0.90-1.12 (m, 2H) 1.32-1.72 (m, 10H) 1.97-2.12 (m, 2H) 3.58 (s, 3H) 7.19-7.35 (m, 5H); MS (APCI+) m/z 247 (M+H)+. cooled to −78° C. Stirred the reaction at −78° C. to slowly warm to room temperature overnight After 15 hrs the reaction mixture was quenched with 10% aq NH4Cl (50 mL) extracted with ethyl acetate (100 mL) The organic extract was washed with H2O (50 mL) and brine dried over Na2SO4 filtered concentrated by rotary evaporation The residue was purified by SiO2 flash chromatography with 2:3 dichloromethane/hexanes

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 2-phenyl-propionic acid methyl ester (3.0 g, 18.27 mmol) in tetrahydrofuran (25 mL) at −78° C. was treated dropwise with the lithium hexamethyldisilazide (21.9 mL, 1M in tetrahydrofuran, 21.9 mmol) and stirred for 1 hour. Bromomethyl-cyclohexane (3.09 mL, 21.92 mmol) was added to the reaction and the reaction was allowed to warm to 25° C. and stirred for 18 hours. The solvent was removed in vacuo and the residue was partitioned between water and ethyl acetate. The aqueous phase was extracted three times with ethyl acetate and the ethyl acetate layers were combined, dried with sodium sulfate, filtered, and concentrated in vacuo. The residue was chromatographed on silica gel eluting with hexane, then 2.5% ethyl acetate in hexane, and 5% ethyl acetate in hexane to give the title compound (4.02 g, 84%). 1H NMR (300 MHz, CDCl3): δ ppm 1.11 (m, 10H) 1.55 (m, 4H) 1.80 (m, 1H) 2.04 (m, 1H) 3.64 (m, 3H) 7.29 (m, 5H). stirred for 18 hours The solvent was removed in vacuo the residue was partitioned between water and ethyl acetate The aqueous phase was extracted three times with ethyl acetate dried with sodium sulfate filtered concentrated in vacuo The residue was chromatographed on silica gel eluting with hexane

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

Procedure: 2-Phenylpropionic acid (8.4 g, 56 mmol) in methanol (180 ml) and concentrated H2SO4 (2 ml) were heated at reflux for 4 hours. The reaction was cooled down to room temperature and concentrated in vacuo (~30 ml), which was poured into ice water (~100 ml). The products were extracted with Et2O (150 ml×3), which was washed with saturated NaHCO3, H2O and dried over MgSO4. Filtration and evaporation of solvent yielded a yellow oil (8.9 g), which was distilled to give a colorless oil (8.34 g, 51 mmol, 91%, b.p. 73° C./1.5 mm Hg). at reflux for 4 hours concentrated in vacuo (~30 ml), which was poured into ice water (~100 ml) The products were extracted with Et2O (150 ml×3), which was washed with saturated NaHCO3, H2O dried over MgSO4 Filtration and evaporation of solvent