methyl 2-(4-chlorophenyl)propanoate

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

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

Procedure: 35 ml of a 1.6 molar solution of n-butyllithium in hexane 10 (61 mmol) are added dropwise to a solution of 8.1 ml of diisopropylamine (85 mmol)l in 20 ml tetrahydrofuran at −78° C. Then a solution of 10.0 g (50 mmol) of methyl 2-(4-chloro-phenyl)-propionate in 30 ml tetrahydrofuran is added dropwise at −78° C. Formaldehyde gas is then piped into the reaction mixture at −20° C. for 30 minutes. After the addition of 5% citric acid and glacial acetic acid the mixture is extracted with ethyl acetate. The organic phases are washed with 1N sulphuric acid, water, saturated sodium bicarbonate solution and saline solution and dried over magnesium sulphate. The crude product is purified on silica gel, eluting with cyclohexane/ethyl acetate (19:1; 9:1; is extracted with ethyl acetate The organic phases are washed with 1N sulphuric acid, water, saturated sodium bicarbonate solution and saline solution dried over magnesium sulphate The crude product is purified on silica gel eluting with cyclohexane/ethyl acetate (19:1

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

Procedure: 35 ml of a 1.6 molar solution of n-butyllithium in hexane 10 (61 mmol) are added dropwise to a solution of 8.1 ml of diisopropylamine (85 mmol)l in 20 ml tetrahydrofuran at −78° C. Then a solution of 10.0 g (50 mmol) of methyl 2-(4-chloro-phenyl)-propionate in 30 ml tetrahydrofuran is added dropwise at −78° C. Formaldehyde gas is then piped into the reaction mixture at −20° C. for 30 minutes. After the addition of 5% citric acid and glacial acetic acid the mixture is extracted with ethyl acetate. The organic phases are washed with 1N sulphuric acid, water, saturated sodium bicarbonate solution and saline solution and dried over magnesium sulphate. The crude product is purified on silica gel, eluting with cyclohexane/ethyl acetate (19:1; 9:1; is extracted with ethyl acetate The organic phases are washed with 1N sulphuric acid, water, saturated sodium bicarbonate solution and saline solution dried over magnesium sulphate The crude product is purified on silica gel eluting with cyclohexane/ethyl acetate (19:1

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

Procedure: Lithium hydroxide (0.17 g, 7.10 mmol) was added to a stirred solution of 2-(4-chloro-phenyl)-propionic acid methyl ester (0.47 g, 2.366 mmol) in tetrahydrofuran, water and methanol (4:1:1, 12 ml). The mixture was stirred overnight and the volatiles evaporated in vacuo. The mixture was basified by addition of aqueous sodium hydrogencarbonate and washed with ethyl acetate. The aqueous was then acidified with 2M HCl and the product extracted into ethyl acetate. The organic phase was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to give the desired product. Yield 0.4 g, 91%. NMR 1H (300 MHz, DMSO): 1.36 (d, 3H), 3.72 (q, 1H), 7.23-7.38 (m, 4ArH), 12.48 (bs, 1H). the volatiles evaporated in vacuo The mixture was basified by addition of aqueous sodium hydrogencarbonate washed with ethyl acetate the product extracted into ethyl acetate The organic phase was washed with brine dried over anhydrous magnesium sulfate filtered concentrated in vacuo

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

Procedure: The same reaction and the same treatment as in Example 1 were followed using methyl p-chlorophenylacetate and methyl bromide, producing methyl p-chloro(α-methyl)phenylacetate in a yield of 83% and p-chloro(α-methyl)phenylacetic acid in a yield of 5%. The spectral data of the ester were as follows. The same reaction

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

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

Procedure: Lithium hydroxide (0.17 g, 7.10 mmol) was added to a stirred solution of 2-(4-chloro-phenyl)-propionic acid methyl ester (0.47 g, 2.366 mmol) in tetrahydrofuran, water and:methanol (4:1:1, 12 ml). The mixture was stirred overnight and the volatiles evaporated in vacuo. The mixture was basified by addition of aqueous sodium hydrogencarbonate and washed with ethyl acetate. The aqueous was then acidified with 2M HCl and the product extracted into ethyl acetate. The organic phase was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to give the desired product. Yield 0.4 g, 91%. NMR 1H (300 MHz, DMSO): 1.36 (d, 3H), 3.72 (q, 1H), 7.23-7.38 (m, 4ArH), 12.48 (bs, 1H). the volatiles evaporated in vacuo The mixture was basified by addition of aqueous sodium hydrogencarbonate washed with ethyl acetate the product extracted into ethyl acetate The organic phase was washed with brine dried over anhydrous magnesium sulfate filtered concentrated in vacuo

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

Procedure: Methyl 2-(4-chlorophenyl)propanoate (1.50 g, 7.55 mmol) was dissolved in THF (14 mL) and cooled to 0° C. The solution was treated with KOtBu (85 mg, 0.755 mmol) and allowed to stir for 15 minutes. The solution was cooled to −78° C. and then treated with the acrylate (1.22 mL, 8.31 mmol). The mixture was allowed to stir overnight to room temperature to completion by TLC analysis. The mixture was then quenched with saturated NH4Cl. The THF was removed in vacuo to afford a yellow oil. The residue was partitioned between ethyl acetate and water. The aqueous was extracted with ethyl acetate, and the organics were combined. The organic portion was washed with water, then brine, separated, dried over MgSO4, filtered, and concentrated in vacuo to afford the crude material as a yellow oil. The material was purified by chromatography (silica gel eluted with 90:10 hexanes:ethyl acetate, Rf=0.35) to afford 5-tert-butyl 1-methyl 2-(4-chlorophenyl)-2-methylpentanedioate as a colorless oil (1.69 g, 69%). This 5-tert-butyl 1-methyl 2-(4-chlorophenyl)-2-methylpentanedioate (1.69 g, 5.17 mmol) was dissolved in TFA (15.9 mL; 207 mmol) at room temperature and allowed to stir for 2 hours to completion by LCMS (neg) analysis. The solution was concentrated in vacuo to afford 4-(4-chlorophenyl)-5-methoxy-4-methyl-5-oxopentanoic acid as a colorless oil (1.42 g, 100%). The solution was cooled to −78° C. to stir overnight to room temperature to completion by TLC analysis The mixture was then quenched with saturated NH4Cl The THF was removed in vacuo to afford a yellow oil The residue was partitioned between ethyl acetate and water The aqueous was extracted with ethyl acetate The organic portion was washed with water brine, separated dried over MgSO4 filtered concentrated in vacuo to afford the crude material as a yellow oil The material was purified by chromatography (silica gel eluted with 90:10 hexanes:ethyl acetate, Rf=0.35)

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

Procedure: Methyl 2-(4-chlorophenyl)propanoate (1.50 g, 7.55 mmol) was dissolved in THF (14 mL) and cooled to 0° C. The solution was treated with KOtBu (85 mg, 0.755 mmol) and allowed to stir for 15 minutes. The solution was cooled to −78° C. and then treated with the acrylate (1.22 mL, 8.31 mmol). The mixture was allowed to stir overnight to room temperature to completion by TLC analysis. The mixture was then quenched with saturated NH4Cl. The THF was removed in vacuo to afford a yellow oil. The residue was partitioned between ethyl acetate and water. The aqueous was extracted with ethyl acetate, and the organics were combined. The organic portion was washed with water, then brine, separated, dried over MgSO4, filtered, and concentrated in vacuo to afford the crude material as a yellow oil. The material was purified by chromatography (silica gel eluted with 90:10 hexanes:ethyl acetate, Rf=0.35) to afford 5-tert-butyl 1-methyl 2-(4-chlorophenyl)-2-methylpentanedioate as a colorless oil (1.69 g, 69%). This 5-tert-butyl 1-methyl 2-(4-chlorophenyl)-2-methylpentanedioate (1.69 g, 5.17 mmol) was dissolved in TFA (15.9 mL; 207 mmol) at room temperature and allowed to stir for 2 hours to completion by LCMS (neg) analysis. The solution was concentrated in vacuo to afford 4-(4-chlorophenyl)-5-methoxy-4-methyl-5-oxopentanoic acid as a colorless oil (1.42 g, 100%). The solution was cooled to −78° C. to stir overnight to room temperature to completion by TLC analysis The mixture was then quenched with saturated NH4Cl The THF was removed in vacuo to afford a yellow oil The residue was partitioned between ethyl acetate and water The aqueous was extracted with ethyl acetate The organic portion was washed with water brine, separated dried over MgSO4 filtered concentrated in vacuo to afford the crude material as a yellow oil The material was purified by chromatography (silica gel eluted with 90:10 hexanes:ethyl acetate, Rf=0.35)

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

Procedure: 35 ml of a 1.6 molaric solution of n-butyl lithium (61 mmol) in hexane were dropped to a solution of 8.1 ml (85 mmol) of diisopropylamine in 20 ml of tetrahydrofurane at −78° C. Subsequently, a solution of 10.0 g (50 mmol) of methyl 2-(4-chloro-phenyl)-propionate in 30 ml of tetrahydrofurane were dropped into the reaction mixture at −78° C. and subsequenty formaldehyde was introduced as gas at −20° C. within 30 minutes. The reaction mixture was extracted with ethyl acetate after addition of 5 percent citric acid and glacial acetic acid. The organic phase was washed with IN sulfuric acid, water, saturated sodium bicarbonate solution and sodium chloride solution and died over magnesium sulfate. The raw product was purified over silica gel whereby the eluation was carried out with cyclohexane/ethyl acetate (19:1; 9:1; 4:1; 1:1; and 0:1). The uniform fractions were combined and evaporated down. The reaction mixture was extracted with ethyl acetate after addition of 5 percent citric acid and glacial acetic acid The organic phase was washed with IN sulfuric acid, water, saturated sodium bicarbonate solution and sodium chloride solution The raw product was purified over silica gel whereby the eluation evaporated down

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

Procedure: Lithium hydroxide (0.17 g, 7.10 mmol) was added to a stirred solution of 2-(4-chloro-phenyl)-propionic acid methyl ester (0.47 g, 2.366 mmol) in tetrahydrofuran, water and methanol (4:1:1, 12 ml). The mixture was stirred overnight and the volatiles evaporated in vacuo. The mixture was basified by addition of aqueous sodium hydrogencarbonate and washed with ethyl acetate. The aqueous was then acidified with 2M HCl and the product extracted into ethyl acetate. The organic phase was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to give the desired product. Yield 0.4 g, 91%. NMR 1H (300 MHz, DMSO): 1.36 (d, 3H), 3.72 (q, 1H), 7.23-7.38 (m, 4ArH), 12.48 (bs, 1H). the volatiles evaporated in vacuo The mixture was basified by addition of aqueous sodium hydrogencarbonate washed with ethyl acetate the product extracted into ethyl acetate The organic phase was washed with brine dried over anhydrous magnesium sulfate filtered concentrated in vacuo

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

Procedure: 35 ml of a 1.6 molar solution of n-butyllithium in hexane (61 mmol) are added dropwise to a solution of 8.1 ml of diisopropylamine (85 mmol) in 20 ml of tetrahydrofuran at −78° C. Then a solution of 10.0 g (50 mmol) of methyl 2-(4-chloro-phenyl)-propionate in 30 ml of tetrahydrofuran is added dropwise at −78° C. Gaseous formaldehyde is piped into the reaction mixture at −20° C. for 30 minutes. After the addition of 5% citric acid and glacial acetic acid the mixture is extracted with ethyl acetate. The organic phases are washed with 1N sulphuric acid, water, saturated sodium bicarbonate solution and saline solution and dried over magnesium sulphate. The crude product is purified on silica gel, eluting with cyclohexane/ethyl acetate (19:1; 9:1; 4:1; 1:1 and 0:1). The uniform fractions are combined and concentrated by evaporation. is extracted with ethyl acetate The organic phases are washed with 1N sulphuric acid, water, saturated sodium bicarbonate solution and saline solution dried over magnesium sulphate The crude product is purified on silica gel eluting with cyclohexane/ethyl acetate (19:1; 9:1; 4:1; 1:1 and 0:1) concentrated by evaporation