Oxalyl chloride → 4-(Benzyloxy)-5-bromo-2-methylbenzoyl chloride

To a suspension of 4-(benzyloxy)-5-bromo-2-methylbenzoic acid (16.6 g, 51.7 mmol) in chloroform (80 mL), oxalyl chloride (5 mL, 56.9 mmol) and N,N-dimethylformamide (6 drops) were added and stirred at room temperature for 1 hour. The reaction mixture was concentrated to give 4-(benzyloxy)-5-bromo-2-methylbenzoyl chloride. Next, to a suspension of N,O-dimethylhydroxylamine hydrochloride (5.55 g, 56.9 mmol) and triethylamine (15 mL, 103 mmol) in chloroform (60 mL), a solution of 4-(benzyloxy)-5-bromo-2-methylbenzoyl chloride in chloroform (60 mL) was added dropwise under ice cooling and stirred at room temperature for 1 hour, followed by addition of water and chloroform under ice cooling to separate the organic layer. The organic layer was washed with saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride, and then dried over anhydrous magnesium sulfate. After filtering off the desiccant, the solvent was distilled off under reduced pressure to give 4-(benzyloxy)-5-bromo-N-methoxy-N-dimethylbenzamide. To a solution of this product in THF (150 mL), lithium aluminum hydride (1.96 g, 51.7 mmol) was added at −10° C. and stirred at the same temperature for 1 hour. The reaction mixture was diluted with 1N hydrochloric acid, followed by addition of ethyl acetate to separate the organic layer. The organic layer was washed with 1N hydrochloric acid, saturated sodium bicarbonate and saturated aqueous sodium chloride, and then dried over anhydrous magnesium sulfate. After filtering off the desiccant, the solvent was distilled off under reduced pressure to give 4-(benzyloxy)-5-bromo-2-methylbenzaldehyde. To a solution of this product in toluene (120 mL), ethylene glycol (30 mL, 517 mmol) and p-toluenesulfonic acid monohydrate (0.50 g, 2.58 mmol) were added and heated under reflux for 1.5 hours using a Dean-Stark apparatus. Ethyl acetate was added to the reaction mixture to separate the organic layer. The organic layer was washed with water, saturated sodium bicarbonate and saturated aqueous sodium chloride, and then dried over anhydrous magnesium sulfate. After filtering off the desiccant, the solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=5:1) and further purified by NH-type silica gel column chromatography (chloroform) to give the titled compound (12.8 g, 71%, 3 steps) as a colorless powder.