1,3-dibromo-5-methoxybenzene

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: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: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: To a solution of 1,3-dibromo-5-methoxy-benzene (20.7 g, 78 mmol) in dry THF (100 mL) was added under nitrogen a 1.6 M solution of nBuLi in hexane (48.7 mL, 78 mmol) at such a rate that the reaction temperature did not rise above −50° C. After the addition the mixture was cooled to −70° C. and acetone (6.86 mL, 78 mmol) was added over a 5 min period. After 2 min the reaction was quenched with saturated NH4Cl solution and stirred for 10 min. The mixture was diluted with water and extracted with TBME. The organic layer was dried with MgSO4, filtered and evaporated. Chromatographic purification over silica gel (hexane-EtOAc 95:5 to 85:15) provided impure 2-(3-bromo-5-methoxy-phenyl)-propan-2-ol as a yellow oil: TLC (hexane-AcOEt 6:1) Rf=0.22; HPLC RtH1=2.35 min; ESIMS [M−OH]−=227,229; 1H NMR (400 MHz, CDCl3): δ 7.27 (t, 1H), 7.02 (dd, 1H), 6.97 (dd, 1H), 3.83 (s, 3H), 1.59 (s, 6H). This material was treated with (±) camphor sulfonic acid (70 mg) in refluxing hexane with the azeotropical removal of water. After 1 h the cooled reaction mixture is diluted with TBME, washed with 5% aq. NaHCO3, dried with MgSO4, filtered and evaporated. Chromatographic purification over silica gel (hexane-toluene 0-10%) gave impure 1-bromo-3-iso-propenyl-5-methoxy-benzene as a slightly yellow oil: 1H NMR (400 MHz, CDCl3): δ 7.27 (t, 1H), 7.07 (s, 1H), 6.99 (s, 1H), 5.48 (s, 1H), 5.16 (s, 1H), 3.75 (s, 3H), 2.07 (s, 3H). This material was stirred in the presence of Ra—Ni catalyst (5 g) in EtOH (15 mL) under a hydrogen atmosphere for 18 h. The mixture was filtered over a bed of Celite and evaporated to obtain a yellow oil that contained still some starting material. It was taken up in CH2Cl2 (10 mL) and treated with meta-chlorperbenzoic acid (250 mg). The mixture was washed with sodium sulfite solution, followed by water and evaporated. Chromatography over silica gel (hexane-CH2Cl2 100:1 to 9:1) gave the title compound as a colorless oil: TLC (hexane-EtOAc 9:1) Rf=0.50; HPLC RtH1=3.79 min; 1H NMR (400 MHz, CDCl3): δ 6.97 (t, 1H), 6.86 (t, 1H), 6.69 (t, 1H), 3.78 (s, 3H), 2.84 (heptet, 1H), 1.22 (d, 6H). did not rise above −50° C After the addition the mixture After 2 min the reaction was quenched with saturated NH4Cl solution The mixture was diluted with water extracted with TBME The organic layer was dried with MgSO4 filtered evaporated Chromatographic purification over silica gel (hexane-EtOAc 95:5 to 85:15)

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

実験手順: A similar procedure as described in Example 47, step 2 was used, starting from 3,5-dibromoanisole (5.3 g, 19.93 mmol) and sodium 1-propanethiolate (2.47 g, 23.92 mmol) to afford 1-bromo-3-methoxy-5-propylsulfanyl-benzene (2.01 g, 39%) as a light yellow oil: EI(+)-HRMS m/e calcd for C10H13BrOS (M)+ 259.9870, found 259.9870.

反応条件: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture 1,3-dibromo-5-methoxy-benzene (2.65 g, 10 mmol) and sodium thioethoxide (1.01 g, 12 mmol) was added dimethylformamide (30 mL) at room temperature. Then, the resulting light yellow solution was heated to 105° C. and stirred for 2 h at which time TLC analysis of the mixture indicated the absence of starting material. The reaction mixture was cooled to room temperature and diluted with water (50 mL) and brine solution (50 mL). Then, the organic compound was extracted into ethyl acetate (3×50 mL). The combined extracts were washed with brine solution (150 mL) and dried over anhydrous magnesium sulfate. Filtration of the drying agent and the concentration of the solution under reduced pressure gave the crude residue which was purified by using an ISCO 120 g column chromatography, eluting with 0-20% ethyl actetate in hexanes to obtain 1-bromo-3-ethylsulfanyl-5-methoxy-benzene (1.35 g, 55%) as a white solid: EI(+)-HRMS m/e calcd for C9H11BrOS (M)+ 245.9715, found 245.9713. The reaction mixture was cooled to room temperature Then, the organic compound was extracted into ethyl acetate (3×50 mL) The combined extracts were washed with brine solution (150 mL) dried over anhydrous magnesium sulfate Filtration of the drying agent the concentration of the solution under reduced pressure gave the crude residue which was purified eluting with 0-20% ethyl actetate in hexanes