2-bromo-5-methoxybenzaldehyde

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a THF (50 ml) solution of 2-bromo-5-methoxybenzaldehyde (10 g) was added dropwise a THF (30 ml) solution of the Grignard reagent prepared from 5-Bromo-1,3-benzodioxole (11.2 g) and Mg (1.6 g). The mixture was stirred for 1 hour at room temperature and ammonium chloride solution was added therein, then extracted with ethyl acetate. The extract was washed with water and dried with magnesium sulfate, then concentrated. The residue was purified with silica gel column (Hex/EA=3/1) to give (2-bromo-5-methoxyphenyl) (1,3-benzodioxol-5-yl)methanol as an oily substance (15 g). (2-bromo-5-methoxyphenyl)(1,3-benzodioxol-5-yl)methanol was dissolved in ether (300 ml) and n-BuLi(1.6M/Hex: 64 ml) was added dropwise at -78° C. The reaction mixture was stirred for 5 minutes at -78° C., then stirred for 1 hour at 0° C. To the mixture was added DMF (30 ml) and stirred for 1 hour at room temperature. To the reaction mixture was added water and extracted with ether. The extract was washed with water and dried with magnesium sulfate then concentrated under reduced pressure. The obtained residue was dissolved in toluene (250 ml) and maleimide (6 g) and p-toluenesulfonic acid monohydrate (1.0 g) were added thereto. The reaction mixture was refluxed for 20 hours and the separated solid was filtered off. The filtrate was concentrated under reduced pressure. To the obtained residue was added concentrated hydrochloric acid and heated under reflux for 1 hour. The mixture was cooled to room temperature and the resultant yellow-brown solid was collected by suction and washed with water, then recrystalized with THF to give the entitled compound (5.4 g). extracted with ethyl acetate The extract was washed with water dried with magnesium sulfate concentrated The residue was purified with silica gel column (Hex/EA=3/1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A stirred solution of 3-methoxybenzaldehyde (27.23 g) in dichloromethane (150 mL) at 0° C. is treated with a solution of bromine (32 g) in dry dichloromethane (50 mL) over 30 minutes. The reaction mixture is stirred at room temperature for 4 hours, combined with a previous preparation carried out on the same scale, and washed with saturated sodium metabisulphite solution (400 mL), with water (400 mL), brine (400 mL) and dried over magnesium sulphate. Evaporation and recrystallisation of the residue from petroleum ether (b.p. 40-60° C.) gives 2-bromo-5-methoxybenzaldehyde (45.25 g) as a white solid, m.p. 73-74° C. combined with a previous preparation washed with saturated sodium metabisulphite solution (400 mL), with water (400 mL), brine (400 mL) dried over magnesium sulphate Evaporation and recrystallisation of the residue from petroleum ether (b.p. 40-60° C.)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-bromo-5-methoxy-benzaldehyde (45.25 g), ethylene glycol (52.22 g) and 4-toluenesulphonic acid (0.4 g) in toluene (400 mL) is heated at reflux for 5 hours using a Dean and Stark apparatus to remove water formed in the reaction. The reaction mixture is washed five times with water (500 mL) and evaporated giving 2-(2-bromo-5-methoxyphenyl)-[1,3]dioxolane (51.9 g) as a yellow liquid. is heated at reflux for 5 hours to remove water formed in the reaction The reaction mixture is washed five times with water (500 mL) evaporated

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 2-bromo-5-methoxybenzaldehyde (1 eq) in dichloroethane was added 3-aminopropanol (1.5 eq) followed by NaBH(OAc)3 (2 eq) and acetic acid (4 eq) and the resulting mixture was stirred at RT under nitrogen for 8 h. The reaction mixture was quenched by careful addition of 2M Na2CO3 solution and stirred 1 h. The mixture was concentrated in vacuo and poured into diethyl ether. The phases were separated and the organic phase washed with 1N HCl solution. The aqueous phase was then washed with diethyl ether and subsequently basified with 1N NaOH solution. The aqueous phase was extracted with diethyl ether, dried over Na2SO4 and concentrated in vacuo to give 3-(((2-bromo-5-methoxyphenyl)methyl) amino)propan-1-ol as a clear oil. EI-MS m/z 274, 276 (M+H)+ The reaction mixture was quenched by careful addition of 2M Na2CO3 solution stirred 1 h The mixture was concentrated in vacuo poured into diethyl ether The phases were separated the organic phase washed with 1N HCl solution The aqueous phase was then washed with diethyl ether The aqueous phase was extracted with diethyl ether dried over Na2SO4 concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Pyridinium Chlorochromate (1.2 eq) was added to a solution of 2-bromo-5-methoxybenzyl alcohol (1 eq) and Celite (1.2 eq) in methylene chloride (0.30 M) at RT and the resulting mixture was stirred under nitrogen for 3 h. The mixture was filtered through a plug of silica rinsing with methylene chloride and concentrated in vacuo to give 2-bromo-5-methoxy benzaldehyde as a white solid. EI-MS m/z 232, 234 (M+NH4)+ The mixture was filtered through a plug of silica rinsing with methylene chloride concentrated in vacuo