methyl 5-bromo-2,2-dimethylpentanoate

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: A mixture of 11.3 g (49.6 mmol) of 3,5-dimethyl-4-(phenylmethoxy)phenol (Example G), 13.3 g (1.2×49.6 mmol) of 5-bromo-2,2-dimethylvaleric acid, methyl ester (U.S. Pat. No. 4,665,226) and 8.2 g (1.2×49.6 mmol) of anhydrous potassium carbonate in 300 mL of acetonitrile is stirred at reflux for 18 hours. The reaction flask and inorganic residue are washed with fresh acetonitrile and the solvent is removed. A diethyl ether solution of the residual product is washed with 50 mL of 2N potassium hydroxide solution, brine, dried and evaporated leaving 20.6 g of the product as a pale yellow oil. Distillation through a short path apparatus affords 15.4 g of the title compound; bp 190°-194° C./0.1 mm (230°-240° C). at reflux for 18 hours The reaction flask and inorganic residue are washed with fresh acetonitrile the solvent is removed A diethyl ether solution of the residual product is washed with 50 mL of 2N potassium hydroxide solution, brine dried evaporated

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

実験手順: A 2-1, 3 neck, round bottom flask equipped with an overhead stirrer is charged with 29.4 g (12mmol) of 2,3,5-trimethyl-4-(phenylmethoxy)phenol (Example C), 29.8 g (1.1×12.1 mmol) of 5-bromo-2,2-dimethylvaleric acid, methyl ester (U.S. Pat. No. 4,665,226), 20.1 g (1.2×121 mmol) of anhydrous potassium carbonate and 300 mL of acetonitrile. The heterogeneous mixture is stirred at reflux for 96 hours. The solid is removed and the reaction flask and filtered solids are washed with fresh acetonitrile, the solvent removed and the residue taken up in 500 mL of hexane. On standing the product crystallizes partially and a seed crystal is retained. The solution is diluted to 700 mL with hexane and warmed to dissolve the product. After washing with 2×75 mL of 2N potassium hydroxide solution, and brine the solution is dried and evaporated leaving 46.5 g of a pale yellow solid. This crystallizes from 500 mL of hexane in the presence of charcoal and the solution is cooled to 0° C. and seeded to afford 41.4 g of the title compound as a colorless solid; mp 67°-68° C. A 2-1, 3 neck, round bottom flask equipped with an overhead stirrer at reflux for 96 hours The solid is removed the reaction flask and filtered solids are washed with fresh acetonitrile the solvent removed crystallizes partially The solution is diluted to 700 mL with hexane warmed to dissolve the product After washing with 2×75 mL of 2N potassium hydroxide solution, and brine the solution is dried evaporated

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

実験手順: A 500 mL, 3 neck round bottom flask is charged with 7.6 g (50 mmol) of 4-methoxy-2,5-xylenol, 8.3 g (60 mmol) of anhydrous potassium carbonate 13.4 g (60 mmol) of 5-bromo-2,2-dimethylvaleric acid, methyl ester (U.S. Pat. No. 4,665,226) and 150 mL of acetonitrile. The mixture is stirred mechanically at reflux for 24 hours. The reaction flask and inorganic solids are washed with fresh acetonitrile and the filtrate evaporated. The residue is taken up in diethyl ether and the solution washed with 50 mL of 2N potassium hydroxide solution, brine, dried (magnesium sulfate) and evaporated. The crude product amounts to 16.6 g. Distillation through a short path apparatus first at aspirator pressure and then at 0.5 mm affords 12.9 g of the title compound; infrared spectrum (IR) (C=0) 1732 cm-1. at reflux for 24 hours The reaction flask and inorganic solids are washed with fresh acetonitrile the filtrate evaporated the solution washed with 50 mL of 2N potassium hydroxide solution, brine dried (magnesium sulfate) evaporated Distillation through a short path apparatus first at aspirator pressure

反応条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 48.9 g (0.4 mol) of 4-hydroxybenzaldehyde in 600 ml of dimethylformamide was stirred under a nitrogen atmosphere. Sodium hydride (31.2 g; 0.44 mol) was added to the stirring solution over 45 minutes. The temperature of the reaction mixture was maintained at 35°-40° during the addition, and stirring was continued for an additional 45 minutes at room temperature. Methyl 5-bromo-2,2-dimethylpentanoate (98.1 g; 0.44 mol), was added dropwise over 20 minutes. The reaction temperature was maintained at 40° during the addition. After addition was complete, the temperature was raised to 65° C. and stirring was continued at 65° C. for 31/2 hours. After standing overnight, the dimethylformamide was removed on a rotary evaporator and the residue was taken up in water and ether. The aqueous layer was extracted a second time with ether and the combined extracts were washed, dried, and concentrated under reduced pressure. The residue was triturated two times with n-heptane. The heptane insoluble oil was distilled via a short path apparatus to give methyl 5-[4-formylphenoxy)-2,2-dimethyl-pentanoate: bp 143°-144° C. at 0.03 mm of Hg; yield 39.4 g (37%). Additional analytically pure product was obtained from the heptane extract: 32.3 g (31%). Anal. Calcd. for C15H20O4 : The temperature of the reaction mixture was maintained at 35°-40° during the addition The reaction temperature was maintained at 40° during the addition After addition stirring was continued at 65° C. for 31 2 hours After standing overnight the dimethylformamide was removed on a rotary evaporator The aqueous layer was extracted a second time with ether the combined extracts were washed dried concentrated under reduced pressure The residue was triturated two times with n-heptane The heptane insoluble oil was distilled via a short path apparatus

反応条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 48.9 g (0.4 mol) of 4-hydroxybenzaldehyde in 600 ml of dimethylformamide was stirred under a nitrogen atmosphere. Sodium hydride (31.2 g; 0.44 mol) was added to the stirring solution over 45 minutes. The temperature of the reaction mixture was maintained at 35°-40° during the addition, and stirring was continued for an additional 45 minutes at room temperature. Methyl 5-bromo-2,2-dimethylpentanoate (98.1 g; 0.44 mol), was added dropwise over 20 minutes. The reaction temperature was maintained at 40° during the addition. After addition was complete, the temperature was raised to 65° C. and stirring was continued at 65° C. for 31/2 hours. After standing overnight, the dimethylformamide was removed on a rotary evaporator and the residue was taken up in water and ether. The aqueous layer was extracted a second time with ether and the combined extracts were washed, dried, and concentrated under reduced pressure. The residue was triturated two times with n-heptane. The heptane insoluble oil was distilled via a short path apparatus to give methyl 5-[4-formylphenoxy)-2,2-dimethyl-pentanoate: bp 143°-144° C. at 0.03 mm of Hg; yield 39.4 g (37%). Additional analytically pure product was obtained from the heptane extract: 32.3 g (31%). Anal. Calcd. for C15H20O4 : The temperature of the reaction mixture was maintained at 35°-40° during the addition The reaction temperature was maintained at 40° during the addition After addition stirring was continued at 65° C. for 31 2 hours After standing overnight the dimethylformamide was removed on a rotary evaporator The aqueous layer was extracted a second time with ether the combined extracts were washed dried concentrated under reduced pressure The residue was triturated two times with n-heptane The heptane insoluble oil was distilled via a short path apparatus

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

実験手順: A mixture of 11.3 g (49.6 mmol) of 3,5-dimethyl-4-(phenylmethoxy)phenol (Example G), 13.3 g (1.2×49.6 mmol) of 5-bromo-2,2-dimethylvaleric acid, methyl ester (U.S. Pat. No. 4,665,226) and 8.2 g (1.2×49.6 mmol) of anhydrous potassium carbonate in 300 mL of acetonitrile is stirred at reflux for 18 hours. The reaction flask and inorganic residue are washed with fresh acetonitrile and the solvent is removed. A diethyl ether solution of the residual product is washed with 50 mL of 2N potassium hydroxide solution, brine, dried and evaporated leaving 20.6 g of the product as a pale yellow oil. Distillation through a short path apparatus affords 15.4 g of the title compound; bp 190°-194° C./0.1 mm (230°-240° C). at reflux for 18 hours The reaction flask and inorganic residue are washed with fresh acetonitrile the solvent is removed A diethyl ether solution of the residual product is washed with 50 mL of 2N potassium hydroxide solution, brine dried evaporated

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

実験手順: A 2-1, 3 neck, round bottom flask equipped with an overhead stirrer is charged with 29.4 g (12mmol) of 2,3,5-trimethyl-4-(phenylmethoxy)phenol (Example C), 29.8 g (1.1×12.1 mmol) of 5-bromo-2,2-dimethylvaleric acid, methyl ester (U.S. Pat. No. 4,665,226), 20.1 g (1.2×121 mmol) of anhydrous potassium carbonate and 300 mL of acetonitrile. The heterogeneous mixture is stirred at reflux for 96 hours. The solid is removed and the reaction flask and filtered solids are washed with fresh acetonitrile, the solvent removed and the residue taken up in 500 mL of hexane. On standing the product crystallizes partially and a seed crystal is retained. The solution is diluted to 700 mL with hexane and warmed to dissolve the product. After washing with 2×75 mL of 2N potassium hydroxide solution, and brine the solution is dried and evaporated leaving 46.5 g of a pale yellow solid. This crystallizes from 500 mL of hexane in the presence of charcoal and the solution is cooled to 0° C. and seeded to afford 41.4 g of the title compound as a colorless solid; mp 67°-68° C. A 2-1, 3 neck, round bottom flask equipped with an overhead stirrer at reflux for 96 hours The solid is removed the reaction flask and filtered solids are washed with fresh acetonitrile the solvent removed crystallizes partially The solution is diluted to 700 mL with hexane warmed to dissolve the product After washing with 2×75 mL of 2N potassium hydroxide solution, and brine the solution is dried evaporated

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

実験手順: A 2-1, 3 neck, round bottom flask equipped with an overhead stirrer is charged with 29.4 g (12mmol) of 2,3,5-trimethyl-4-(phenylmethoxy)phenol (Example C), 29.8 g (1.1×12.1 mmol) of 5-bromo-2,2-dimethylvaleric acid, methyl ester (U.S. Pat. No. 4,665,226), 20.1 g (1.2×121 mmol) of anhydrous potassium carbonate and 300 mL of acetonitrile. The heterogeneous mixture is stirred at reflux for 96 hours. The solid is removed and the reaction flask and filtered solids are washed with fresh acetonitrile, the solvent removed and the residue taken up in 500 mL of hexane. On standing the product crystallizes partially and a seed crystal is retained. The solution is diluted to 700 mL with hexane and warmed to dissolve the product. After washing with 2×75 mL of 2N potassium hydroxide solution, and brine the solution is dried and evaporated leaving 46.5 g of a pale yellow solid. This crystallizes from 500 mL of hexane in the presence of charcoal and the solution is cooled to 0° C. and seeded to afford 41.4 g of the title compound as a colorless solid; mp 67°-68° C. A 2-1, 3 neck, round bottom flask equipped with an overhead stirrer at reflux for 96 hours The solid is removed the reaction flask and filtered solids are washed with fresh acetonitrile the solvent removed crystallizes partially The solution is diluted to 700 mL with hexane warmed to dissolve the product After washing with 2×75 mL of 2N potassium hydroxide solution, and brine the solution is dried evaporated

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

実験手順: A 500 mL, 3 neck round bottom flask is charged with 7.6 g (50 mmol) of 4-methoxy-2,5-xylenol, 8.3 g (60 mmol) of anhydrous potassium carbonate 13.4 g (60 mmol) of 5-bromo-2,2-dimethylvaleric acid, methyl ester (U.S. Pat. No. 4,665,226) and 150 mL of acetonitrile. The mixture is stirred mechanically at reflux for 24 hours. The reaction flask and inorganic solids are washed with fresh acetonitrile and the filtrate evaporated. The residue is taken up in diethyl ether and the solution washed with 50 mL of 2N potassium hydroxide solution, brine, dried (magnesium sulfate) and evaporated. The crude product amounts to 16.6 g. Distillation through a short path apparatus first at aspirator pressure and then at 0.5 mm affords 12.9 g of the title compound; infrared spectrum (IR) (C=0) 1732 cm-1. at reflux for 24 hours The reaction flask and inorganic solids are washed with fresh acetonitrile the filtrate evaporated the solution washed with 50 mL of 2N potassium hydroxide solution, brine dried (magnesium sulfate) evaporated Distillation through a short path apparatus first at aspirator pressure

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

実験手順: A 500 mL, 3 neck round bottom flask is charged with 7.6 g (50 mmol) of 4-methoxy-2,5-xylenol, 8.3 g (60 mmol) of anhydrous potassium carbonate 13.4 g (60 mmol) of 5-bromo-2,2-dimethylvaleric acid, methyl ester (U.S. Pat. No. 4,665,226) and 150 mL of acetonitrile. The mixture is stirred mechanically at reflux for 24 hours. The reaction flask and inorganic solids are washed with fresh acetonitrile and the filtrate evaporated. The residue is taken up in diethyl ether and the solution washed with 50 mL of 2N potassium hydroxide solution, brine, dried (magnesium sulfate) and evaporated. The crude product amounts to 16.6 g. Distillation through a short path apparatus first at aspirator pressure and then at 0.5 mm affords 12.9 g of the title compound; infrared spectrum (IR) (C=0) 1732 cm-1. at reflux for 24 hours The reaction flask and inorganic solids are washed with fresh acetonitrile the filtrate evaporated the solution washed with 50 mL of 2N potassium hydroxide solution, brine dried (magnesium sulfate) evaporated Distillation through a short path apparatus first at aspirator pressure