2,4-dibromo-6-methylphenol

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

実験手順: A solution of 2,4-dibromo-6-methylphenol (2.0 g, 7.5 mmol), 3-bromo-2-methylprop-1-ene (1.5 g, 11.3 mmol), K2CO3 (3.12 g, 22.6 mmol) in DMF (15 mL) was heated at 70° C. 2 hours. The reaction was then cooled to room temperature and was diluted with water and hexanes. The layers were separated and the organic layer was dried over sodium sulfate, filtered and concentrated. The residue was purified on a silica gel column eluting with a gradient of 0-10% EtOAc/hexanes to give the title intermediate (1.05 g) as colorless liquid. 2 hours The layers were separated the organic layer was dried over sodium sulfate filtered concentrated The residue was purified on a silica gel column eluting with a gradient of 0-10% EtOAc/hexanes

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

実験手順: To a stirred solution of the product of stage (a) (266 g) in 4 N aqueous sodium hydroxide (900 ml), dimethyl sulphate (192 ml) was added whilst maintaining the temperature at 35°-40° C. The mixture was stirred for 5 minutes, then 4 N aqueous sodium hydroxide (450 ml) was added and dimethyl sulphate (96 ml) was added dropwise. The temperature rose to 55° C. The mixture was then stirred overnight, and the product was extracted into dichloromethane, washed with water, dried over magnesium sulphate, filtered, and the solvent evaporated off to give a brown oil (280 g). Distillation gave the title product as a colourless oil, bp 96°-98° C./0.3 mm Hg. whilst maintaining the temperature at 35°-40° C rose to 55° C The mixture was then stirred overnight the product was extracted into dichloromethane washed with water dried over magnesium sulphate filtered the solvent evaporated off

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

実験手順: To a stirred solution of the product of stage (a) (266 g) in 4 N aqueous sodium hydroxide (900 ml), dimethyl sulphate (192 ml) was added whilst maintaining the temperature at 35°-40° C. The mixture was stirred for 5 minutes, then 4 N aqueous sodium hydroxide (450 ml) was added and dimethyl sulphate (96 ml) was added dropwise. The temperature rose to 55° C. The mixture was then stirred overnight, and the product was extracted into dichloromethane, washed with water, dried over magnesium sulphate, filtered, and the solvent evaporated off to give a brown oil (280 g). Distillation gave the title product as a colourless oil, bp 96°-98° C./0.3 mm Hg. whilst maintaining the temperature at 35°-40° C rose to 55° C The mixture was then stirred overnight the product was extracted into dichloromethane washed with water dried over magnesium sulphate filtered the solvent evaporated off

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

実験手順: A solution of 2,4-dibromo-6-methylphenol (2.0 g, 7.5 mmol), 3-bromo-2-methylprop-1-ene (1.5 g, 11.3 mmol), K2CO3 (3.12 g, 22.6 mmol) in DMF (15 mL) was heated at 70° C. 2 hours. The reaction was then cooled to room temperature and was diluted with water and hexanes. The layers were separated and the organic layer was dried over sodium sulfate, filtered and concentrated. The residue was purified on a silica gel column eluting with a gradient of 0-10% EtOAc/hexanes to give the title intermediate (1.05 g) as colorless liquid. 2 hours The layers were separated the organic layer was dried over sodium sulfate filtered concentrated The residue was purified on a silica gel column eluting with a gradient of 0-10% EtOAc/hexanes

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

実験手順: To a stirred solution of the product of stage (a) (266 g) in 4 N aqueous sodium hydroxide (900 ml), dimethyl sulphate (192 ml) was added whilst maintaining the temperature at 35°-40° C. The mixture was stirred for 5 minutes, then 4 N aqueous sodium hydroxide (450 ml) was added and dimethyl sulphate (96 ml) was added dropwise. The temperature rose to 55° C. The mixture was then stirred overnight, and the product was extracted into dichloromethane, washed with water, dried over magnesium sulphate, filtered, and the solvent evaporated off to give a brown oil (280 g). Distillation gave the title product as a colourless oil, bp 96°-98° C./0.3 mm Hg. whilst maintaining the temperature at 35°-40° C rose to 55° C The mixture was then stirred overnight the product was extracted into dichloromethane washed with water dried over magnesium sulphate filtered the solvent evaporated off

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

実験手順: A solution of 2,4-dibromo-6-methyl-phenol (Compound 3,62 g, 0.23 mol) in 700 mL of acetone was treated with potassium carbonate (38.7 g, 0.28 mol), sodium iodide (3.4 g, 0.023 mol) and 3-chloro-2-methylpropene (34 mL, 0.35 mol) and the resulting suspension was refluxed for 18 hours. The solids were filtered and the filtrate was evaporated in vacuo to afford the title compound as a dark yellow oil. 1H-NMR (300 MHz, CDCl3): δ 7.53(d, 1H, J=2.7 Hz), 7.27(d, 1H, J=1.9 Hz), 5.17(s, 1H), 5.02(s, 1H), 4.28(s, 2H), 2.30(s, 3H), 1.92(s, 3H). the resulting suspension was refluxed for 18 hours The solids were filtered the filtrate was evaporated in vacuo

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

実験手順: To a stirred solution of the product of stage (a) (266 g) in 4 N aqueous sodium hydroxide (900 ml), dimethyl sulphate (192 ml) was added whilst maintaining the temperature at 35°-40° C. The mixture was stirred for 5 minutes, then 4 N aqueous sodium hydroxide (450 ml) was added and dimethyl sulphate (96 ml) was added dropwise. The temperature rose to 55° C. The mixture was then stirred overnight, and the product was extracted into dichloromethane, washed with water, dried over magnesium sulphate, filtered, and the solvent evaporated off to give a brown oil (280 g). Distillation gave the title product as a colourless oil, bp 96°-98° C./0.3 mm Hg. whilst maintaining the temperature at 35°-40° C rose to 55° C The mixture was then stirred overnight the product was extracted into dichloromethane washed with water dried over magnesium sulphate filtered the solvent evaporated off

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

実験手順: A solution of 2,4-dibromo-6-methylphenol (2.0 g, 7.5 mmol), 3-bromo-2-methylprop-1-ene (1.5 g, 11.3 mmol), K2CO3 (3.12 g, 22.6 mmol) in DMF (15 mL) was heated at 70° C. 2 hours. The reaction was then cooled to room temperature and was diluted with water and hexanes. The layers were separated and the organic layer was dried over sodium sulfate, filtered and concentrated. The residue was purified on a silica gel column eluting with a gradient of 0-10% EtOAc/hexanes to give the title intermediate (1.05 g) as colorless liquid. 2 hours The layers were separated the organic layer was dried over sodium sulfate filtered concentrated The residue was purified on a silica gel column eluting with a gradient of 0-10% EtOAc/hexanes