Chloromethyl Methyl Ether → 1-Chloro-2-fluoro-3-(methoxymethoxy)benzene

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A solution of 51.3 g (350 mmole) of 3-fluoro-4-chlorophenol in 700 mL of CH2Cl2 under N2 was prepared and cooled to 5° C. The stirred mixture was treated with 35.3 mL (37.5 g, 465 mmole) of chloromethyl methyl ether. The reactor was equipped with a thermocouple and an addition funnel. To the stirred mixture was added dropwise 61 mL of DIEA (45.2 g, 350 mmole) such that the temperature did not exceed 10° C. After 30 min, an additional 30 mL of DIEA was added dropwise. After a total of 1 h, an additional 30 mL of DIEA was added. The mixture was allowed to stand overnight. The solution was washed with 900 mL of 1N HCl and the aqueous layer extracted three times with Et2O. Combined extracts were dried with Mg2SO4, carefully concd and distilled in vacuo 78-81° C. @ 9 torr to afford 62.5 g (93.7%) of a clear, colorless liquid: 1H NMR (CDCl3/400 MHz) 3.46 (s, 3H), 5.13 (s, 2H), 6.77 (ddd, J=1H, 8.9 Hz, 2.8 Hz, 1.3 Hz), 6.87 (dd, 1H, J=10.7 Hz, 2.8 Hz), 7.26 (t, 1H, J=8.7 Hz); 19F NMR (CDCl3/400 MHz) −113.5 (t, 1F, J=9.7 Hz); 13C NMR (CDCl3/100 MHz) 56.1, 94.6, 105.2 (d, J=24.2 Hz), 112.8 (d, J=3.4 Hz), 130.5 (d, J=1.1 Hz), 156.9 (d, J=9.7 Hz), 158.3 (d, J=248.1 Hz); MS (EI+) 190 (M+, 12), 129 (8), 117 (8), 45 (100); HRMS (EI) m/z calcd for (C8H8O2ClF) 190.0197, found 190.0175.

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