2-chloro-3-methoxybenzaldehyde

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:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-chloro-3-methoxybenzaldehyde 7a (4.65 g, 27.3 mmol) and methyl (methylthio)methyl sulfoxide (4.3 mL, 43.9 mmol) in THF (25 mL) was added a 40% methanolic solution of Triton B (6.2 mL, 13.6 mmol) and the resulting solution was refluxed for 16 hours. After THF was removed, the residue was taken up in ethyl acetate, washed with 1 N HCl, H2O, and brine, then was dried over Na2SO4, and concentrated. Purification by column chromatography on silica gel with dichloromethane afforded 2-chloro-1-methoxy-3-[2-(methylsulfanyl)-2-(methylsulfinyl)vinyl]benzene 7b (3.61 g, 48% ) as a yellow oil. GCMS (El) m/z 225 (M+-Cl-16), 210 (M+-Cl—OMe). the resulting solution was refluxed for 16 hours After THF was removed washed with 1 N HCl, H2O, and brine was dried over Na2SO4 concentrated Purification by column chromatography on silica gel with dichloromethane

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

実験手順: To a solution of 2-chloro-3-hydroxybenzaldehyde (4.55 g, 29 mmol) in DMF (30 mL) was added K2CO3 (4.8 g, 34.9 mmol) followed by MeI (2.7 mL, 43.6 mmol), and the mixture was stirred at room temperature for 16 hours. Following concentration in vacuo, the residual was taken up in ethyl acetate, washed with H2O, brine, dried over Na2SO4, and concentrated. Purification by column chromatography on silica gel with ethyl acetate/hexanes 1/5 afforded 2-chloro-3-methoxybenzaldehyde 7a (4.68 g, 94%) as a colorless oil, which solidified upon standing. GCMS (EI) m/z 170, 172 (M+). concentration in vacuo washed with H2O, brine dried over Na2SO4 concentrated Purification by column chromatography on silica gel with ethyl acetate/hexanes 1/5 afforded 2-chloro-3-methoxybenzaldehyde 7a (4.68 g, 94%) as a colorless oil, which

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

実験手順: To a sol. of N,N′,N′-trimethylethylendiamine (2.77 g, 21.4 mmol) in toluene (50 mL) was added BuLi (13.0 mL, 20.8 mmol) dropwise at 0° C. After stirring for 15 min at 0° C., m-anisaldehyde (2.44 g, 20 mmol) was added, and the mixture was stirred 30 min at 0° C. PhLi (30 mL, 60 mmol) was then added at 0° C., and the mixture was stirred at rt for 4 h. The mixture was cooled to −30° C., and 25 mL THF were added followed by hexachloroethane (14.2 g, 60 mmol) in THF (25 mL). The cooling bath was removed and the mixture was stirred for 3 h. Then it was poured with stirring onto aq. 5M HCl (20 mL). The aq. layer was extracted with EtOAc (2×). The combined org. extracts were washed successively with aq. 1M NaOH, aq. 1M HCl, and brine. The org. layer was dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the crude by FC (EtOAc/heptane 5:95→1:9) afforded the desired aldehyde, which was further purified by crystallization (EtOAc/heptane, 0° C.) to give 1.50 g of pure title product. LC-MS: tR=0.88 min. the mixture was stirred 30 min at 0° C the mixture was stirred at rt for 4 h The mixture was cooled to −30° C. The cooling bath was removed the mixture was stirred for 3 h Then it was poured with stirring onto aq. 5M HCl (20 mL) The aq. layer was extracted with EtOAc (2×) extracts were washed successively with aq. 1M NaOH, aq. 1M HCl, and brine layer was dried over MgSO4 filtered the solvents were removed under reduced pressure Purification of the crude by FC (EtOAc/heptane 5:95→1:9)

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

実験手順: 3-Chloroperoxybenzoic acid (760 mg, 4.396 mmol) was added portionwise to a solution of 2-Chloro-3-Methoxybenzaldehyde (500 mg, 2.931 mmol) in dichloromethane (12 ml) and the mixture was stirred for 3 hours at room temperature. Further 3-chloroperoxybenzoic acid (760 mg, 4.396 mmol) was added and mixture allowed to stir for 18 hrs. The solution was diluted with 12 ml dichloromethane and washed with saturated sodium sulphite solution (15 ml) and saturated sodium hydrogen carbonate solution (15 ml). The organic layer was dried over sodium sulphate and concentrated in vacuo to a yellow gum. The residue was dissolved in methanol (12 ml), triethylamine (0.05 ml) was added and the mixture stirred for 18 hours at room temperature. The solution was concentrated in vacuo, dissolved in diethyl ether (20 ml) and extracted with 1N sodium hydroxide (20 ml). The aqueous layer was acidified to pH1 by dropwise addition of 2N hydrochloric acid and extracted with diethyl ether (2×25 ml). These combined organic layers were dried over sodium sulphate and concentrated in vacuo to afford the title compound as a brown gum in 70% yield, 325 mg. to stir for 18 hrs washed with saturated sodium sulphite solution (15 ml) and saturated sodium hydrogen carbonate solution (15 ml) The organic layer was dried over sodium sulphate concentrated in vacuo to a yellow gum The residue was dissolved in methanol (12 ml) triethylamine (0.05 ml) was added the mixture stirred for 18 hours at room temperature The solution was concentrated in vacuo dissolved in diethyl ether (20 ml) extracted with 1N sodium hydroxide (20 ml) The aqueous layer was acidified to pH1 by dropwise addition of 2N hydrochloric acid extracted with diethyl ether (2×25 ml) These combined organic layers were dried over sodium sulphate concentrated in vacuo

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

実験手順: 3-Chloroperoxybenzoic acid (760 mg, 4.396 mmol) was added portionwise to a solution of 2-Chloro-3-Methoxybenzaldehyde (500 mg, 2.931 mmol) in dichloromethane (12 ml) and the mixture was stirred for 3 hours at room temperature. Further 3-chloroperoxybenzoic acid (760 mg, 4.396 mmol) was added and mixture allowed to stir for 18 hrs. The solution was diluted with 12 ml dichloromethane and washed with saturated sodium sulphite solution (15 ml) and saturated sodium hydrogen carbonate solution (15 ml). The organic layer was dried over sodium sulphate and concentrated in vacuo to a yellow gum. The residue was dissolved in methanol (12 ml), triethylamine (0.05 ml) was added and the mixture stirred for 18 hours at room temperature. The solution was concentrated in vacuo, dissolved in diethyl ether (20 ml) and extracted with 1N sodium hydroxide (20 ml). The aqueous layer was acidified to pH1 by dropwise addition of 2N hydrochloric acid and extracted with diethyl ether (2×25 ml). These combined organic layers were dried over sodium sulphate and concentrated in vacuo to afford the title compound as a brown gum in 70% yield, 325 mg. to stir for 18 hrs washed with saturated sodium sulphite solution (15 ml) and saturated sodium hydrogen carbonate solution (15 ml) The organic layer was dried over sodium sulphate concentrated in vacuo to a yellow gum The residue was dissolved in methanol (12 ml) triethylamine (0.05 ml) was added the mixture stirred for 18 hours at room temperature The solution was concentrated in vacuo dissolved in diethyl ether (20 ml) extracted with 1N sodium hydroxide (20 ml) The aqueous layer was acidified to pH1 by dropwise addition of 2N hydrochloric acid extracted with diethyl ether (2×25 ml) These combined organic layers were dried over sodium sulphate concentrated in vacuo

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

実験手順: 3-Chloroperoxybenzoic acid (760 mg, 4.396 mmol) was added portionwise to a solution of 2-Chloro-3-Methoxybenzaldehyde (500 mg, 2.931 mmol) in dichloromethane (12 ml) and the mixture was stirred for 3 hours at room temperature. Further 3-chloroperoxybenzoic acid (760 mg, 4.396 mmol) was added and mixture allowed to stir for 18 hrs. The solution was diluted with 12 ml dichloromethane and washed with saturated sodium sulphite solution (15 ml) and saturated sodium hydrogen carbonate solution (15 ml). The organic layer was dried over sodium sulphate and concentrated in vacuo to a yellow gum. The residue was dissolved in methanol (12 ml), triethylamine (0.05 ml) was added and the mixture stirred for 18 hours at room temperature. The solution was concentrated in vacuo, dissolved in diethyl ether (20 ml) and extracted with 1N sodium hydroxide (20 ml). The aqueous layer was acidified to pH1 by dropwise addition of 2N hydrochloric acid and extracted with diethyl ether (2×25 ml). These combined organic layers were dried over sodium sulphate and concentrated in vacuo to afford the title compound as a brown gum in 70% yield, 325 mg. to stir for 18 hrs washed with saturated sodium sulphite solution (15 ml) and saturated sodium hydrogen carbonate solution (15 ml) The organic layer was dried over sodium sulphate concentrated in vacuo to a yellow gum The residue was dissolved in methanol (12 ml) triethylamine (0.05 ml) was added the mixture stirred for 18 hours at room temperature The solution was concentrated in vacuo dissolved in diethyl ether (20 ml) extracted with 1N sodium hydroxide (20 ml) The aqueous layer was acidified to pH1 by dropwise addition of 2N hydrochloric acid extracted with diethyl ether (2×25 ml) These combined organic layers were dried over sodium sulphate concentrated in vacuo

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

実験手順: To a solution of 2-chloro-3-methoxybenzaldehyde 7a (4.65 g, 27.3 mmol) and methyl (methylthio)methyl sulfoxide (4.3 mL, 43.9 mmol) in THF (25 mL) was added a 40% methanolic solution of Triton B (6.2 mL, 13.6 mmol) and the resulting solution was refluxed for 16 hours. After THF was removed, the residue was taken up in ethyl acetate, washed with 1 N HCl, H2O, and brine, then was dried over Na2SO4, and concentrated. Purification by column chromatography on silica gel with dichloromethane afforded 2-chloro-1-methoxy-3-[2-(methylsulfanyl)-2-(methylsulfinyl)vinyl]benzene 7b (3.61 g, 48% ) as a yellow oil. GCMS (El) m/z 225 (M+-Cl-16), 210 (M+-Cl—OMe). the resulting solution was refluxed for 16 hours After THF was removed washed with 1 N HCl, H2O, and brine was dried over Na2SO4 concentrated Purification by column chromatography on silica gel with dichloromethane

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

実験手順: To a solution of 2-chloro-3-hydroxybenzaldehyde (4.55 g, 29 mmol) in DMF (30 mL) was added K2CO3 (4.8 g, 34.9 mmol) followed by MeI (2.7 mL, 43.6 mmol), and the mixture was stirred at room temperature for 16 hours. Following concentration in vacuo, the residual was taken up in ethyl acetate, washed with H2O, brine, dried over Na2SO4, and concentrated. Purification by column chromatography on silica gel with ethyl acetate/hexanes 1/5 afforded 2-chloro-3-methoxybenzaldehyde 7a (4.68 g, 94%) as a colorless oil, which solidified upon standing. GCMS (EI) m/z 170, 172 (M+). concentration in vacuo washed with H2O, brine dried over Na2SO4 concentrated Purification by column chromatography on silica gel with ethyl acetate/hexanes 1/5 afforded 2-chloro-3-methoxybenzaldehyde 7a (4.68 g, 94%) as a colorless oil, which

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

実験手順: To a solution of 2-chloro-3-methoxybenzaldehyde 7a (4.65 g, 27.3 mmol) and methyl (methylthio)methyl sulfoxide (4.3 mL, 43.9 mmol) in THF (25 mL) was added a 40% methanolic solution of Triton B (6.2 mL, 13.6 mmol) and the resulting solution was refluxed for 16 hours. After THF was removed, the residue was taken up in ethyl acetate, washed with 1 N HCl, H2O, and brine, then was dried over Na2SO4, and concentrated. Purification by column chromatography on silica gel with dichloromethane afforded 2-chloro-1-methoxy-3-[2-(methylsulfanyl)-2-(methylsulfinyl)vinyl]benzene 7b (3.61 g, 48% ) as a yellow oil. GCMS (El) m/z 225 (M+-Cl-16), 210 (M+-Cl—OMe). the resulting solution was refluxed for 16 hours After THF was removed washed with 1 N HCl, H2O, and brine was dried over Na2SO4 concentrated Purification by column chromatography on silica gel with dichloromethane

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

実験手順: To a solution of 2-chloro-3-methoxybenzaldehyde 7a (4.65 g, 27.3 mmol) and methyl (methylthio)methyl sulfoxide (4.3 mL, 43.9 mmol) in THF (25 mL) was added a 40% methanolic solution of Triton B (6.2 mL, 13.6 mmol) and the resulting solution was refluxed for 16 hours. After THF was removed, the residue was taken up in ethyl acetate,washed with 1 N HCl, H2O, and brine, then was dried over Na2SO4, and concentrated. Purification by column chromatography on silica gel with dichloromethane afforded 2-chloro-1-methoxy-3-[2-methylsulfanyl)-2-(methylsulfinyl)vinyl]benzene 7b (3.61 g, 48%) as a yellow oil. GCMS (EI) m/z 225 (M+-Cl16), 210 (M+-Cl-OMe). the resulting solution was refluxed for 16 hours After THF was removed was dried over Na2SO4 concentrated Purification by column chromatography on silica gel with dichloromethane