Pyridine → 2-Bromo-4-(chloromethyl)-1-(methoxymethoxy)benzene

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Reaction Steps

(3-Bromo-4-methoxymethoxy-phenyl)-methanol (250 mg) was dissolved in DCM (20 mL), pyridine (0.15 mL) was added followed by thionyl chloride (0.15 mL), and the mixture was stirred for 1 hour. The mixture was partitioned with water and ethyl acetate. The solvent removal gave 2-bromo-4-chloromethyl-1-methoxymethoxy-benzene as a clear oil, which was used directly in next step. The oil was dissolved in acetone, and sodium iodide (300 mg) was added. The mixture was stirred overnight and a yellow precipitate was formed. Extraction with ethyl acetate and water gave 2-iodo-4-chloromethyl-1-methoxymethoxy-benzene as a brown oil that turned into solid after standing. 1HNMR (CDCl3, 300 MHz): 7.58 (d, J=2.0 Hz, 1H), 7.25 (dd, J=2.0, 8.5 Hz, 1H), 7.07 (d, J=8.5 Hz, 1H), 5.25 (s, 2H), 4.39(s, 2H), 3.51 (s, 3H) ppm. The iodide (170 mg) and trimethylphosphate (0.1 mL) were mixed and stirred at 120° C. for 1 hour. After cooling to room temperature, the reaction mixture was directly applied to silica gel column eluting with 5% MeOH in DCM to yield 150 mg of the corresponding phosphonate.

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