ethyl 2-(2-chlorophenyl)acetate

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of ethyl 2-(2-chlorophenyl)acetate (11.32 g, 57.0 mmol), ethyl 4-bromobutanoate (33.3 g, 171 mmol) and Cs2CO3 (55.7 g, 171 mmol) in DMF (Volume: 57.0 ml) was heated at 60° C. overnight. The reaction was cooled to RT and diluted into a mixture of ethyl acetate and water. The organic layer was separated, and the aqueous layer was extracted three times with EtOAc. The combined organic layers were concentrated in vacuo. The residue was purified by flash chromatography (SG, 0 to 45% EtOAc/Hex) to get diethyl 2-(2-chlorophenyl)hexanedioate (17.82 g, 57.0 mmol, 100% yield). LC-MS (M+H)+=313.2. 1H NMR (500 MHz, CD3OD) δ 7.41 (ddd, J=17.0, 7.7, 1.5 Hz, 2H), 7.33-7.24 (m, 2H), 4.21-4.07 (m, 4H), 2.34 (td, J=7.3, 2.1 Hz, 2H), 2.16-2.05 (m, 1H), 1.82 (dddd, J=13.4, 10.3, 7.7, 5.5 Hz, 1H), 1.70-1.48 (m, 2H), 1.33-1.25 (m, 1H), 1.24 (t, J=7.2, 7.2 Hz, 3H), 1.21 (t, J=7.2 Hz, 3H). The reaction was cooled to RT The organic layer was separated the aqueous layer was extracted three times with EtOAc The combined organic layers were concentrated in vacuo The residue was purified by flash chromatography (SG, 0 to 45% EtOAc/Hex)

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of ethyl 2-(2-chlorophenyl)acetate (11.32 g, 57.0 mmol), ethyl 4-bromobutanoate (33.3 g, 171 mmol) and Cs2CO3 (55.7 g, 171 mmol) in DMF (Volume: 57.0 ml) was heated at 60° C. overnight. The reaction was cooled to RT and diluted into a mixture of ethyl acetate and water. The organic layer was separated, and the aqueous layer was extracted three times with EtOAc. The combined organic layers were concentrated in vacuo. The residue was purified by flash chromatography (SG, 0 to 45% EtOAc/Hex) to get diethyl 2-(2-chlorophenyl)hexanedioate (17.82 g, 57.0 mmol, 100% yield). LC-MS (M+H)+=313.2. 1H NMR (500 MHz, CD3OD) δ 7.41 (ddd, J=17.0, 7.7, 1.5 Hz, 2H), 7.33-7.24 (m, 2H), 4.21-4.07 (m, 4H), 2.34 (td, J=7.3, 2.1 Hz, 2H), 2.16-2.05 (m, 1H), 1.82 (dddd, J=13.4, 10.3, 7.7, 5.5 Hz, 1H), 1.70-1.48 (m, 2H), 1.33-1.25 (m, 1H), 1.24 (t, J=7.2, 7.2 Hz, 3H), 1.21 (t, J=7.2 Hz, 3H). The reaction was cooled to RT The organic layer was separated the aqueous layer was extracted three times with EtOAc The combined organic layers were concentrated in vacuo The residue was purified by flash chromatography (SG, 0 to 45% EtOAc/Hex)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2-(2-chlorophenyl)acetic acid (10 g, 58.6 mmol) in EtOH (Volume: 152 ml) was treated with H2SO4 (1.719 ml, 32.2 mmol). The result mixture was refluxed overnight. The heat was removed, and the reaction mixture was concentrated. The resulting oil was dissolved in EtOAc and CAREFULLY treated with aqueous Na2CO3 (3.47 g, 32.8 mmol) (CAUTION: Gas evolution) until the solution remained basic and no further gas evolution was seen. The EtOAc layer was then removed and the aqueous layer was again extracted two times with EtOAc. The combined organic layers were then washed with brine, dried over Na2SO4 and concentrated in vacuo to obtain ethyl 2-(2-chlorophenyl)acetate (11.32 g, 57.0 mmol, 97% yield). LC-MS (M+H)+=199.1. The result mixture was refluxed overnight The heat was removed the reaction mixture was concentrated The resulting oil was dissolved in EtOAc The EtOAc layer was then removed the aqueous layer was again extracted two times with EtOAc The combined organic layers were then washed with brine dried over Na2SO4 concentrated in vacuo

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of ethyl 2-(2-chlorophenyl)acetate (11.32 g, 57.0 mmol), ethyl 4-bromobutanoate (33.3 g, 171 mmol) and Cs2CO3 (55.7 g, 171 mmol) in DMF (Volume: 57.0 ml) was heated at 60° C. overnight. The reaction was cooled to RT and diluted into a mixture of ethyl acetate and water. The organic layer was separated, and the aqueous layer was extracted three times with EtOAc. The combined organic layers were concentrated in vacuo. The residue was purified by flash chromatography (SG, 0 to 45% EtOAc/Hex) to get diethyl 2-(2-chlorophenyl)hexanedioate (17.82 g, 57.0 mmol, 100% yield). LC-MS (M+H)+=313.2. 1H NMR (500 MHz, CD3OD) δ 7.41 (ddd, J=17.0, 7.7, 1.5 Hz, 2H), 7.33-7.24 (m, 2H), 4.21-4.07 (m, 4H), 2.34 (td, J=7.3, 2.1 Hz, 2H), 2.16-2.05 (m, 1H), 1.82 (dddd, J=13.4, 10.3, 7.7, 5.5 Hz, 1H), 1.70-1.48 (m, 2H), 1.33-1.25 (m, 1H), 1.24 (t, J=7.2, 7.2 Hz, 3H), 1.21 (t, J=7.2 Hz, 3H). The reaction was cooled to RT The organic layer was separated the aqueous layer was extracted three times with EtOAc The combined organic layers were concentrated in vacuo The residue was purified by flash chromatography (SG, 0 to 45% EtOAc/Hex)

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of ethyl 2-(2-chlorophenyl)acetate (11.32 g, 57.0 mmol), ethyl 4-bromobutanoate (33.3 g, 171 mmol) and Cs2CO3 (55.7 g, 171 mmol) in DMF (Volume: 57.0 ml) was heated at 60° C. overnight. The reaction was cooled to RT and diluted into a mixture of ethyl acetate and water. The organic layer was separated, and the aqueous layer was extracted three times with EtOAc. The combined organic layers were concentrated in vacuo. The residue was purified by flash chromatography (SG, 0 to 45% EtOAc/Hex) to get diethyl 2-(2-chlorophenyl)hexanedioate (17.82 g, 57.0 mmol, 100% yield). LC-MS (M+H)+=313.2. 1H NMR (500 MHz, CD3OD) δ 7.41 (ddd, J=17.0, 7.7, 1.5 Hz, 2H), 7.33-7.24 (m, 2H), 4.21-4.07 (m, 4H), 2.34 (td, J=7.3, 2.1 Hz, 2H), 2.16-2.05 (m, 1H), 1.82 (dddd, J=13.4, 10.3, 7.7, 5.5 Hz, 1H), 1.70-1.48 (m, 2H), 1.33-1.25 (m, 1H), 1.24 (t, J=7.2, 7.2 Hz, 3H), 1.21 (t, J=7.2 Hz, 3H). The reaction was cooled to RT The organic layer was separated the aqueous layer was extracted three times with EtOAc The combined organic layers were concentrated in vacuo The residue was purified by flash chromatography (SG, 0 to 45% EtOAc/Hex)

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of ethyl 2-(2-chlorophenyl)acetate (11.32 g, 57.0 mmol), ethyl 4-bromobutanoate (33.3 g, 171 mmol) and Cs2CO3 (55.7 g, 171 mmol) in DMF (Volume: 57.0 ml) was heated at 60° C. overnight. The reaction was cooled to RT and diluted into a mixture of ethyl acetate and water. The organic layer was separated, and the aqueous layer was extracted three times with EtOAc. The combined organic layers were concentrated in vacuo. The residue was purified by flash chromatography (SG, 0 to 45% EtOAc/Hex) to get diethyl 2-(2-chlorophenyl)hexanedioate (17.82 g, 57.0 mmol, 100% yield). LC-MS (M+H)+=313.2. 1H NMR (500 MHz, CD3OD) δ 7.41 (ddd, J=17.0, 7.7, 1.5 Hz, 2H), 7.33-7.24 (m, 2H), 4.21-4.07 (m, 4H), 2.34 (td, J=7.3, 2.1 Hz, 2H), 2.16-2.05 (m, 1H), 1.82 (dddd, J=13.4, 10.3, 7.7, 5.5 Hz, 1H), 1.70-1.48 (m, 2H), 1.33-1.25 (m, 1H), 1.24 (t, J=7.2, 7.2 Hz, 3H), 1.21 (t, J=7.2 Hz, 3H). The reaction was cooled to RT The organic layer was separated the aqueous layer was extracted three times with EtOAc The combined organic layers were concentrated in vacuo The residue was purified by flash chromatography (SG, 0 to 45% EtOAc/Hex)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2-(2-chlorophenyl)acetic acid (10 g, 58.6 mmol) in EtOH (Volume: 152 ml) was treated with H2SO4 (1.719 ml, 32.2 mmol). The result mixture was refluxed overnight. The heat was removed, and the reaction mixture was concentrated. The resulting oil was dissolved in EtOAc and CAREFULLY treated with aqueous Na2CO3 (3.47 g, 32.8 mmol) (CAUTION: Gas evolution) until the solution remained basic and no further gas evolution was seen. The EtOAc layer was then removed and the aqueous layer was again extracted two times with EtOAc. The combined organic layers were then washed with brine, dried over Na2SO4 and concentrated in vacuo to obtain ethyl 2-(2-chlorophenyl)acetate (11.32 g, 57.0 mmol, 97% yield). LC-MS (M+H)+=199.1. 1H NMR (500 MHz, CD3OD) δ 7.41 (ddd, J=16.8, 5.6, 3.5 Hz, 1H), 7.35 (dd, J=5.5, 3.7 Hz, 1H), 7.28 (dd, J=5.8, 3.7 Hz, 2H), 4.17 (q, J=7.0 Hz, 2H), 3.80 (s, 2H), 1.26 (t, J=7.2 Hz, 3H). The result mixture was refluxed overnight The heat was removed the reaction mixture was concentrated The resulting oil was dissolved in EtOAc The EtOAc layer was then removed the aqueous layer was again extracted two times with EtOAc The combined organic layers were then washed with brine dried over Na2SO4 concentrated in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2-(2-chlorophenyl)acetic acid (10 g, 58.6 mmol) in EtOH (Volume: 152 ml) was treated with H2SO4 (1.719 ml, 32.2 mmol). The result mixture was refluxed overnight. The heat was removed, and the reaction mixture was concentrated. The resulting oil was dissolved in EtOAc and CAREFULLY treated with aqueous Na2CO3 (3.47 g, 32.8 mmol) (CAUTION: Gas evolution) until the solution remained basic and no further gas evolution was seen. The EtOAc layer was then removed and the aqueous layer was again extracted two times with EtOAc. The combined organic layers were then washed with brine, dried over Na2SO4 and concentrated in vacuo to obtain ethyl 2-(2-chlorophenyl)acetate (11.32 g, 57.0 mmol, 97% yield). LC-MS (M+H)+=199.1. 1H NMR (500 MHz, CD3OD) δ 7.41 (ddd, J=16.8, 5.6, 3.5 Hz, 1H), 7.35 (dd, J=5.5, 3.7 Hz, 1H), 7.28 (dd, J=5.8, 3.7 Hz, 2H), 4.17 (q, J=7.0 Hz, 2H), 3.80 (s, 2H), 1.26 (t, J=7.2 Hz, 3H). The result mixture was refluxed overnight The heat was removed the reaction mixture was concentrated The resulting oil was dissolved in EtOAc The EtOAc layer was then removed the aqueous layer was again extracted two times with EtOAc The combined organic layers were then washed with brine dried over Na2SO4 concentrated in vacuo

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 2-chlorophenylacetic acid (10.12 g, 59.3 mmol) in EtOH (150 mL, 2576 mmol) in a 500 mL round bottom flask was treated with concentrated H2SO4 (0.700 mL, 8.28 mmol) and heated at 90° C. for 16 hours. The solution was concentrated in vacuo, diluted with 1N NaOH(aq) (200 mL), and extracted with EtOAc (2×200 mL). The combined organic layers were washed with 1N NaOH(aq) (200 mL), water (100 mL), and brine (100 mL). The organic layer was dried over MgSO4, concentrated, and dried in vacuo to give ethyl 2-(2-chlorophenyl)acetate (11.344 g). MS m/e=217 (M+H)+. The solution was concentrated in vacuo diluted with 1N NaOH(aq) (200 mL) extracted with EtOAc (2×200 mL) The combined organic layers were washed with 1N NaOH(aq) (200 mL), water (100 mL), and brine (100 mL) The organic layer was dried over MgSO4 concentrated dried in vacuo

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 2-chlorophenylacetic acid (10.12 g, 59.3 mmol) in EtOH (150 mL, 2576 mmol) in a 500 mL round bottom flask was treated with concentrated H2SO4 (0.700 mL, 8.28 mmol) and heated at 90° C. for 16 hours. The solution was concentrated in vacuo, diluted with 1N NaOH(aq) (200 mL), and extracted with EtOAc (2×200 mL). The combined organic layers were washed with 1N NaOH(aq) (200 mL), water (100 mL), and brine (100 mL). The organic layer was dried over MgSO4, concentrated, and dried in vacuo to give ethyl 2-(2-chlorophenyl)acetate (11.344 g). MS m/e=217 (M+H)+. The solution was concentrated in vacuo diluted with 1N NaOH(aq) (200 mL) extracted with EtOAc (2×200 mL) The combined organic layers were washed with 1N NaOH(aq) (200 mL), water (100 mL), and brine (100 mL) The organic layer was dried over MgSO4 concentrated dried in vacuo

反応条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: o-Chlorotoluene (1.89 g), ethanol (46 mg), di-tert-butyl peroxide (73 mg, 1 equivalent), and Pd(Xantphos)Cl2 (3.8 mg, 1 mol %) were added into a reaction kettle, into which 10 atm carbon monoxide was introduced. The reaction was heated to 120° C., and stirred at this constant temperature for 16 h. After the reaction was completed, carbon monoxide was discharged, and 82 mg ethyl o-chlorophenylacetate was obtained by column chromatography, in a yield of 83%. 1HNMR (400 MHz, CDCl3) δ 1.24 (t, J=7.2 Hz, 3H), 3.77 (s, 2H), 4.15 (q, J=7.2 Hz, 2H), 7.21-7.24 (m, 2H), 7.28-7.30 (m, 1H), 7.36-7.40 (m, 1H); 13CNMR (100 MHz, CDCl3) δ 14.2, 39.2, 61.0, 126.9, 128.6, 129.5, 131.4, 132.6, 134.6, 170.6; HRMS (ESI) calcd. for C10H11ClNaO2 [M+Na]: 221.0340. found: 221.0343. The ethyl o-chlorophenylacetate obtained was dissolved in 1,4-dioxane. 6 N sodium hydroxide solution was added, and the reaction was heated to 60° C. After 2 h of reaction, the pH value was adjusted to 1 by adding 2 N hydrochloric acid. After removing the organic solvent under reduced pressure, 66 mg product o-chlorophenylacetic acid was obtained by extraction with ethyl acetate, and the yield of hydrolysis was 94%. was introduced

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of ethyl 2-(2-chlorophenyl)acetate (11.32 g, 57.0 mmol), ethyl 4-bromobutanoate (33.3 g, 171 mmol) and Cs2CO3 (55.7 g, 171 mmol) in DMF (Volume: 57.0 ml) was heated at 60° C. overnight. The reaction was cooled to RT and diluted into a mixture of ethyl acetate and water. The organic layer was separated, and the aqueous layer was extracted three times with EtOAc. The combined organic layers were concentrated in vacuo. The residue was purified by flash chromatography (SG, 0 to 45% EtOAc/Hex) to get diethyl 2-(2-chlorophenyl)hexanedioate (17.82 g, 57.0 mmol, 100% yield). LC-MS (M+H)+=313.2. 1H NMR (500 MHz, CD3OD) δ 7.41 (ddd, J=17.0, 7.7, 1.5 Hz, 2H), 7.33-7.24 (m, 2H), 4.21-4.07 (m, 4H), 2.34 (td, J=7.3, 2.1 Hz, 2H), 2.16-2.05 (m, 1H), 1.82 (dddd, J=13.4, 10.3, 7.7, 5.5 Hz, 1H), 1.70-1.48 (m, 2H), 1.33-1.25 (m, 1H), 1.24 (t, J=7.2, 7.2 Hz, 3H), 1.21 (t, J=7.2 Hz, 3H). The reaction was cooled to RT The organic layer was separated the aqueous layer was extracted three times with EtOAc The combined organic layers were concentrated in vacuo The residue was purified by flash chromatography (SG, 0 to 45% EtOAc/Hex)