methyl 4-(2-bromoethyl)benzoate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Carbazole (0.50 g, 2.99 mmol) and sodium hydride (60 wt. % in mineral oil, 0.14 g, 3.59 mmol) were placed under argon and dissolved in 6 mL of anhydrous DMF at room temperature, giving a dark brown solution. Following the evolution of hydrogen gas, 4-(2-bromo-ethyl)benzoic acid methyl ester (26) (0.73 g, 2.99 mmol) in DMF (2 mL) was added and the reaction was stirred at 70° C. for 2 h. The mixture was taken up in ethyl acetate (30 mL) and water (30 mL), the organic layer was separated and the aqueous layer extracted with ethyl acetate (2×10 mL). The combined organic layers were washed with brine (2×25 mL), dried (Na2SO4) and concentrated in vacuo. The residue was purified by MPCC(C18, 10-100% gradient of MeOH in H2O). The product co-eluted with unreacted carbazole. Cold MeOH (8 mL) was added to the product mixture and the suspension was filtered to remove the solid carbazole. The filtrate was concentrated to give the title compound (291 mg, 43%) as a red solid. 1H NMR (400 MHz, CDCl3): δ 8.11 (m, 2H), 7.92 (d, 2H, J=8.0 Hz), 7.43 (m, 2H), 7.30 (m, 2H), 7.25 (m, 4H), 4.55 (t, 2H, J=7.3 Hz), 3.91 (s, 3H), 3.20 (t, 2H, J=7.4 Hz). 13C NMR (100 MHz, CDCl3): δ 167.0, 144.1, 140.1, 123.0, 128.9, 125.8, 122.9, 120.4, 119.4, 110.6, 108.4, 52.1, 44.4, 35.2. ESI-HRMS (m/z): [M+H]+ calcd. for C22H19NO2, 330.1489. found, 330.1460. giving a dark brown solution was added water (30 mL), the organic layer was separated the aqueous layer extracted with ethyl acetate (2×10 mL) The combined organic layers were washed with brine (2×25 mL) dried (Na2SO4) concentrated in vacuo The residue was purified by MPCC(C18, 10-100% gradient of MeOH in H2O) Cold MeOH (8 mL) was added to the product mixture the suspension was filtered to remove the solid carbazole The filtrate was concentrated

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-(2-Bromo-ethyl)-benzoic acid (1.00 g, 4.37 mmol) was dissolved in MeOH (10 mL) and cooled to 0° C. This was followed by dropwise addition of thionyl chloride (0.48 mL, 6.55 mmol). The mixture was refluxed for 2 h, followed by removal of all volatiles by rotary evaporation. The resulting oil was taken up in EtOAc (50 mL) and washed with water (50 mL). The EtOAc portion was separated, dried (Na2SO4) and concentrated to give the product (1.04 g, 98%) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 8.00 (d, 2H, J=6.54 Hz), 7.29 (d, 2H, J=7.1 Hz), 3.92 (s, 3H), 3.59 (t, 2H, J=7.38 Hz), 3.23 (t, 2H, J=7.34 Hz). The mixture was refluxed for 2 h followed by removal of all volatiles by rotary evaporation washed with water (50 mL) The EtOAc portion was separated dried (Na2SO4) concentrated

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

実験手順: A 2 M solution in hexane of trimethylsilyldiazomethane (0.072 mol, 36 mL) was added dropwise to a solution of 4-(bromoethyl)benzoic acid (15 g, 0.065 mol) in DCM (150 mL) and MeOH (36 mL). The resulting solution was stirred at RT for 2 h then was concentrated under reduced pressure to afford the title compound (15.8 g, 98%) as a pale yellow oil. 1H NMR (CDCl3) δ 3.2 (t, 2H), 3.6 (t, 2H), 3.9 (s, 3H), 7.3 (d, 2H), 8.0 (d, 2H). then was concentrated under reduced pressure

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

実験手順: A 2 M solution in hexane of trimethylsilyldiazomethane (0.072 mol, 36 mL) was added dropwise to a solution of 4-(bromoethyl)benzoic acid (15 g, 0.065 mol) in DCM (150 mL) and MeOH (36 mL). The resulting solution was stirred at RT for 2 h then was concentrated under reduced pressure to afford the title compound (15.8 g, 98%) as a pale yellow oil. 1H NMR (CDCl3) δ 3.2 (t, 2H), 3.6 (t, 2H), 3.9 (s, 3H), 7.3 (d, 2H), 8.0 (d, 2H). then was concentrated under reduced pressure

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

実験手順: Bromide 23-2 (0.52 g, 2.14 mmol) and KCN (167 mg, 2.57 mmol) were combined in 10 mL DMSO. After 20 h, at RT and 1.5 h at 70° the reaction mixture was diluted with EtOAc, washed with water, sat. NaHCO3, 10 % KHSO4 and brine, dried (MgSO4), and concentrated providing 23-3 as a yellow solid. Rf 0.23 (30% EtOAc/hexanes). washed with water, sat. NaHCO3, 10 % KHSO4 and brine dried (MgSO4) concentrated

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

実験手順: A solution of 4-(2-bromoethyl)benzoic acid (4.58 g, TCI) in a mixture of dichloromethane (50 ml) and methanol (50 ml) was added dropwise with a 2.0 M solution of (trimethylsilyl)diazomethane in hexane (11.0 ml, ALD) over 10 minutes, and the mixture was stirred at room temperature for 2 hours. The reaction solution was concentrated under reduced pressure, and then the residue was purified by column chromatography (Flash, hexane:ethyl acetate=15:1) to obtain the title compound (Intermediate ia-01, 4.32 g). The reaction solution was concentrated under reduced pressure the residue was purified by column chromatography (Flash, hexane:ethyl acetate=15:1)

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Carbazole (0.50 g, 2.99 mmol) and sodium hydride (60 wt. % in mineral oil, 0.14 g, 3.59 mmol) were placed under argon and dissolved in 6 mL of anhydrous DMF at room temperature, giving a dark brown solution. Following the evolution of hydrogen gas, 4-(2-bromo-ethyl)benzoic acid methyl ester (26) (0.73 g, 2.99 mmol) in DMF (2 mL) was added and the reaction was stirred at 70° C. for 2 h. The mixture was taken up in ethyl acetate (30 mL) and water (30 mL), the organic layer was separated and the aqueous layer extracted with ethyl acetate (2×10 mL). The combined organic layers were washed with brine (2×25 mL), dried (Na2SO4) and concentrated in vacuo. The residue was purified by MPCC(C18, 10-100% gradient of MeOH in H2O). The product co-eluted with unreacted carbazole. Cold MeOH (8 mL) was added to the product mixture and the suspension was filtered to remove the solid carbazole. The filtrate was concentrated to give the title compound (291 mg, 43%) as a red solid. 1H NMR (400 MHz, CDCl3): δ 8.11 (m, 2H), 7.92 (d, 2H, J=8.0 Hz), 7.43 (m, 2H), 7.30 (m, 2H), 7.25 (m, 4H), 4.55 (t, 2H, J=7.3 Hz), 3.91 (s, 3H), 3.20 (t, 2H, J=7.4 Hz). 13C NMR (100 MHz, CDCl3): δ 167.0, 144.1, 140.1, 123.0, 128.9, 125.8, 122.9, 120.4, 119.4, 110.6, 108.4, 52.1, 44.4, 35.2. ESI-HRMS (m/z): [M+H]+ calcd. for C22H19NO2, 330.1489. found, 330.1460. giving a dark brown solution was added water (30 mL), the organic layer was separated the aqueous layer extracted with ethyl acetate (2×10 mL) The combined organic layers were washed with brine (2×25 mL) dried (Na2SO4) concentrated in vacuo The residue was purified by MPCC(C18, 10-100% gradient of MeOH in H2O) Cold MeOH (8 mL) was added to the product mixture the suspension was filtered to remove the solid carbazole The filtrate was concentrated

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Carbazole (0.50 g, 2.99 mmol) and sodium hydride (60 wt. % in mineral oil, 0.14 g, 3.59 mmol) were placed under argon and dissolved in 6 mL of anhydrous DMF at room temperature, giving a dark brown solution. Following the evolution of hydrogen gas, 4-(2-bromo-ethyl)benzoic acid methyl ester (26) (0.73 g, 2.99 mmol) in DMF (2 mL) was added and the reaction was stirred at 70° C. for 2 h. The mixture was taken up in ethyl acetate (30 mL) and water (30 mL), the organic layer was separated and the aqueous layer extracted with ethyl acetate (2×10 mL). The combined organic layers were washed with brine (2×25 mL), dried (Na2SO4) and concentrated in vacuo. The residue was purified by MPCC(C18, 10-100% gradient of MeOH in H2O). The product co-eluted with unreacted carbazole. Cold MeOH (8 mL) was added to the product mixture and the suspension was filtered to remove the solid carbazole. The filtrate was concentrated to give the title compound (291 mg, 43%) as a red solid. 1H NMR (400 MHz, CDCl3): δ 8.11 (m, 2H), 7.92 (d, 2H, J=8.0 Hz), 7.43 (m, 2H), 7.30 (m, 2H), 7.25 (m, 4H), 4.55 (t, 2H, J=7.3 Hz), 3.91 (s, 3H), 3.20 (t, 2H, J=7.4 Hz). 13C NMR (100 MHz, CDCl3): δ 167.0, 144.1, 140.1, 123.0, 128.9, 125.8, 122.9, 120.4, 119.4, 110.6, 108.4, 52.1, 44.4, 35.2. ESI-HRMS (m/z): [M+H]+ calcd. for C22H19NO2, 330.1489. found, 330.1460. giving a dark brown solution was added water (30 mL), the organic layer was separated the aqueous layer extracted with ethyl acetate (2×10 mL) The combined organic layers were washed with brine (2×25 mL) dried (Na2SO4) concentrated in vacuo The residue was purified by MPCC(C18, 10-100% gradient of MeOH in H2O) Cold MeOH (8 mL) was added to the product mixture the suspension was filtered to remove the solid carbazole The filtrate was concentrated

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-(2-Bromo-ethyl)-benzoic acid (1.00 g, 4.37 mmol) was dissolved in MeOH (10 mL) and cooled to 0° C. This was followed by dropwise addition of thionyl chloride (0.48 mL, 6.55 mmol). The mixture was refluxed for 2 h, followed by removal of all volatiles by rotary evaporation. The resulting oil was taken up in EtOAc (50 mL) and washed with water (50 mL). The EtOAc portion was separated, dried (Na2SO4) and concentrated to give the product (1.04 g, 98%) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 8.00 (d, 2H, J=6.54 Hz), 7.29 (d, 2H, J=7.1 Hz), 3.92 (s, 3H), 3.59 (t, 2H, J=7.38 Hz), 3.23 (t, 2H, J=7.34 Hz). The mixture was refluxed for 2 h followed by removal of all volatiles by rotary evaporation washed with water (50 mL) The EtOAc portion was separated dried (Na2SO4) concentrated