2-bromo-5-hydroxy-4-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:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1 Kg of 2-bromo-5-hydroxy-4-methoxy benzaldehyde (B2) and 1.255 Kg of sulfamic acid were added with stirring into a mixture of 4.473 Kg of EtOAc and 8 L of water. The reaction mixture was stirred until all of the solid had dissolved. The reaction mixture was cooled to between −10 and 0° C. An aqueous solution of sodium chlorite was prepared by dissolving 505 g of sodium chlorite in 3 L of water. The sodium chlorite solution was added to the pre-cooled B2 solution at a rate that maintained the reaction temperature under 5° C. After the complete addition of sodium chlorite solution, the reaction mixture was stirred for another hour at 0° C. and was then allowed to warm up to room temperature. The reaction was monitored by TLC. After the TLC analysis showed completion of the reaction, the aqueous layer was separated. The aqueous layer was extracted with EtOAc (1.789 Kg) and the combined organic layer was transferred to another flask and EtOAc was removed by vacuum distillation at 40° C. 6.92 Kg of toluene was added at between 30 to 40° C., the slurry was cooled to between −10 to 0° C. and the precipitate was collected by filtration to give about 950 g (89% (yield) of 2-bromo-5-hydroxy-4-methoxy benzoic acid (B13). 1H NMR (CDCl3) δ 3.95 (3H, s, CH3), 7.22 (1H, s, CH), 7.46 (1H, s, CH). had dissolved The reaction mixture was cooled to between −10 and 0° C the reaction mixture was stirred for another hour at 0° C. to warm up to room temperature completion of the reaction the aqueous layer was separated The aqueous layer was extracted with EtOAc (1.789 Kg) the combined organic layer was transferred to another flask EtOAc was removed by vacuum distillation at 40° C 6.92 Kg of toluene was added at between 30 to 40° C. the slurry was cooled to between −10 to 0° C. the precipitate was collected by filtration

反応条件: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1 Kg of 2-bromo-5-hydroxy-4-methoxy benzaldehyde (B2) and 1.255 Kg of sulfamic acid were added with stirring into a mixture of 4.473 Kg of EtOAc and 8 L of water. The reaction mixture was stirred until all of the solid had dissolved. The reaction mixture was cooled to between −10 and 0° C. An aqueous solution of sodium chlorite was prepared by dissolving 505 g of sodium chlorite in 3 L of water. The sodium chlorite solution was added to the pre-cooled B2 solution at a rate that maintained the reaction temperature under 5° C. After the complete addition of sodium chlorite solution, the reaction mixture was stirred for another hour at 0° C. and was then allowed to warm up to room temperature. The reaction was monitored by TLC. After the TLC analysis showed completion of the reaction, the aqueous layer was separated. The aqueous layer was extracted with EtOAc (1.789 Kg) and the combined organic layer was transferred to another flask and EtOAc was removed by vacuum distillation at 40° C. 6.92 Kg of toluene was added at between 30 to 40° C., the slurry was cooled to between −10 to 0° C. and the precipitate was collected by filtration to give about 950 g (89% (yield) of 2-bromo-5-hydroxy-4-methoxy benzoic acid (B13). 1H NMR (CDCl3) δ 3.95 (3H, s, CH3), 7.22 (1H, s, CH), 7.46 (1H, s, CH). had dissolved The reaction mixture was cooled to between −10 and 0° C the reaction mixture was stirred for another hour at 0° C. to warm up to room temperature completion of the reaction the aqueous layer was separated The aqueous layer was extracted with EtOAc (1.789 Kg) the combined organic layer was transferred to another flask EtOAc was removed by vacuum distillation at 40° C 6.92 Kg of toluene was added at between 30 to 40° C. the slurry was cooled to between −10 to 0° C. the precipitate was collected by filtration

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

実験手順: B2 is benzylated with benzyl bromide and potassium carbonate in DMF to obtain 5-benzyloxy-2-bromo-4-methoxybenzaldehyde (B3).

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

実験手順: B2 is benzylated with benzyl bromide and potassium carbonate in DMF to obtain 5-benzyloxy-2-bromo-4-methoxybenzaldehyde (B3).

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

実験手順: Compound B1 is demethylated in concentrated sulfuric acid to give 2-bromo-5-hydroxy-4-methoxybenzaldehyde (B2).

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Bromo-5-hydroxy-4-methoxybenzaldehyde (25 g, 0.108 mol) and K2CO3 (30 g, 0.216 mol) were added to acetonitrile (250 mL) and flushed with Ar. Benzyl bromide (20 g, 0.12 mol) was added and the mixture was heated under Ar for 20 h at 50° C. After cooling, the mixture was poured into water (200 ml) and extracted with CH2Cl2 (300 mL). The CH2Cl2 was washed with water (3×100 mL), dried and concentrated. Recrystallization with isopropanol: water (3:1) gave 28.8 g (83%) of 2 as a light brown solid. 1H-NMR (400 MHz, CDCl3) dH 3.96 (3H, s, OCH3), 5.16 (2H, s, CH2Ph), 7.07-7.48 (7H, m, ArH+CH2Ph), 10.16 (1H, s, CHO). flushed with Ar After cooling extracted with CH2Cl2 (300 mL) The CH2Cl2 was washed with water (3×100 mL) dried concentrated Recrystallization with isopropanol: water (3:1)

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Bromo-5-hydroxy-4-methoxybenzaldehyde (25 g, 0.108 mol) and K2CO3 (30 g, 0.216 mol) were added to acetonitrile (250 mL) and flushed with Ar. Benzyl bromide (20 g, 0.12 mol) was added and the mixture was heated under Ar for 20 h at 50° C. After cooling, the mixture was poured into water (200 ml) and extracted with CH2Cl2 (300 mL). The CH2Cl2 was washed with water (3×100 mL), dried and concentrated. Recrystallization with isopropanol: water (3:1) gave 28.8 g (83%) of 2 as a light brown solid. 1H-NMR (400 MHz, CDCl3) dH 3.96 (3H, s, OCH3), 5.16 (2H, s, CH2Ph), 7.07-7.48 (7H, m, ArH+CH2Ph), 10.16 (1H, s, CHO). flushed with Ar After cooling extracted with CH2Cl2 (300 mL) The CH2Cl2 was washed with water (3×100 mL) dried concentrated Recrystallization with isopropanol: water (3:1)

反応条件: temp:0.00; pressure:0.00; stir: