2-bromo-1-(chloromethyl)-4-methoxybenzene

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of NaOH (4.9 g), and (Bu)4NI (1 g) in benzene (14 mL) and water (4.9 mL) was heated at 70° C. under argon to obtain a homogeneous mixture. To this mixture was added dropwise a mixture of isobutylaldehyde (10.1 g, 140 mmoles), and the product of Step 1 (25 g, 106 mmoles) in benzene (38 mL). After the addition, the resulting mixture was stirred at 70° C. for 6 h under argon. It was cooled, diluted with water, and extracted with EtOAc (3×150 mL). The combined organic extracts were washed with water, dried (Na2SO4) and concentrated to dryness. This residue was purified by silica gel flash chromatography using 5% EtOAc in hexane. The appropriate fractions (monitored by TLC) were combined and concentrated to dryness to give the desired product (14.9 g, ˜50%). NMR spectrum of the product was consistent for the proposed structure. to obtain a homogeneous mixture To this mixture was added dropwise After the addition It was cooled extracted with EtOAc (3×150 mL) The combined organic extracts were washed with water dried (Na2SO4) concentrated to dryness This residue was purified by silica gel flash chromatography concentrated to dryness