4-(CHLOROMETHYL)-1-(DIFLUOROMETHOXY)-2-METHOXYBENZENE synthesis

Yield:852706-06-0 60%

Reaction Conditions:

with pyridine;methanesulfonyl chloride in dichloromethane at 20; for 11 h;

Steps:

To a cooled solution of Intermediate 62 (1.46 g, 7.1 mmol) in methylene chloride (20 mL) was added pyridine (1.43 g, 18 mmol) and methane sulfonyl chloride (1.57 g, 13.7 mmol). The reaction was stirred at room temperature for 11 hours. The mixture was poured into a saturated solution of sodium bicarbonate (40 mL) and extracted with methylene chloride (2x20 mL). The combined organic extracts were washed with a saturated solution of sodium bicarbonate (2x15 mL), 1N hydrochloric acid (2x15 mL), brine (1x15 mL), dried (Na2SO4), and the solvent removed under reduced pressure. 4- (Chloromethyl)-1-(difluoromethoxy)-2-methoxybenzene was obtained (1.2 g, 60%) as an oil. 8 (250 MHz, CDCI3) : 3.60 (s, 3H); 4.56 (s, 2H); 6.55 (t, JF-H=75. 0 Hz, 1H) ; 6.94 (dd, Je=2. 0 Hz, J2=8.0 Hz, 1H) ; 7.01 (d, J=2.0 Hz, 1H) ; 7.13 (d, J=8. 0 Hz, 1H).

References:

WO2005/58883,2005,A1 Location in patent:Page/Page column 131