2-Bromo-4-methoxy-5-(benzyloxy)benzaldehyde

2-bromo-5-hydroxy-4-methoxybenzaldehyde and then a 2 g (8.70 mmol) under a nitrogen condition dissolved in N, N- dimethylformamide, 87 mL (0.1 M), 1.8 g of potassium carbonate at 0oC (13.1 mmol), benzyl bromide 1.77 g (10.4 mmol) were added sequentially. .After the reaction temperature raised to 25 ° C, and reacted for 5 hours. It was added to 100 mL of ammonium chloride aqueous solution to terminate the reaction and extracted with EtOAc (3 × 30 mL). Washing the organic layer with brine (brine, 10 mL × 2), dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by silica gel column chromatography to give the title compound 5- (benzyloxy) -2-bromo-4-methoxybenzaldehyde 2.73 g (8.53 mmol, 98percent).2-Bromo-5-hydroxy-4-methoxybenzaldehyde (25 g, 0.108 mol) and KTo a solution 2-bromo-5-hydroxy-4-methoxybenzaldehyde (1c) (120 g, 520 mmol) in DMF (1000 mL) was added potassium carbonate (79 g, 572 mmol) and benzyl bromide (68 mL, 572 mmol). The reaction mixture was stirred at room temperature overnight and quenched with water (3000 mL). The solid obtained was collected by filtration, washed with ether and dried under vacuum to furnish 5-(benzyloxy)-2-bromo-4-methoxybenzaldehyde (1d) (113.19 g, 67.9percent) as a white solid, MP 144 °C; General procedure: In an oven dried Schlenk tube, were added alcohol 1 (69.0–199.5 mg, 0.5 mmol), CuI (10 molpercent)and 1, 10-Phenanthroline (20 molpercent) and K3PO4 (2 mmol) followed by the addition of dioxane (2mL) at room temperature under open air atmosphere. The stirred reaction mixture was heated inan oil bath at 80 C for 7–48 h. Progress of the reaction was monitored by TLC till the reaction iscompleted. Then, the reaction mixture was cooled to room temperature, quenched with aqueousNH4Cl solution and then extracted with CH2Cl2 (3 10 mL). The organic layer was washed withsaturated NaCl solution, dried (Na2SO4), and filtered. Evaporation of the solvent under reducedpressure and purification of the crude material by silica gel column chromatography (petroleumether/ethyl acetate) furnished the aldehyde/ketone 2 (61–97percent).To a solution of 2-bromo-5-hydroxy-4-methoxy-benzaldehyde (25 g, 108 mmol) in MeCN (500 mL) was added (chloromethyl)benzene (13.7 g, 108 mmol) and potassium carbonate (29.9 g, 216 mmol). The mixture was heated at 80 °C with stirring for 15 hours. After being cooledrt, the mixture was filtered. The filtrate was concentrated under reduced pressure. The residuewas partitioned between brine and DCM. The organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure to give 5 -(benzyloxy)-2-bromo-4-methoxy- benzaldehyde (34.2 g, 96.9 mmol) which was used in the next step without further purification.

Molecular Weight:321.16
XLogP3:3.5
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:5
Exact Mass:320.00481
Monoisotopic Mass:320.00481
Topological Polar Surface Area:35.5
Heavy Atom Count:19
Complexity:279
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes