5-(Chloromethyl)-2-methoxy-3-(trifluoromethyl)pyridine synthesis

Yield:-

Reaction Conditions:

with trichlorophosphate at 100;Sealed tube;

Steps:

1.17.A

Step A: Preparation of 2-ChIoro-5-(chloromethyl)-3-(trifluoromethyl)pyridine. To a cold solution of 5-(chloromethyl)-2-methoxy-3-(trifluoromethyl)pyridine (0.3 g, 1.33 mmol) in DMF (0.6 mL) was added dropwise POCl₃ (1.02 g, 6.65 mmol). The reaction was stirred for 1 h at 100 °C in a sealed tube. The reaction was cooled to room temperature, and poured onto ice water (10 mL). The reaction was extracted with DCM (thrice) and the combined organic layer was washed with water and brine, dried with MgSO₄ and concentrated. The residue was purified by silica gel column chromatography to provide the title compound (0.20 g). LCMS m/z = 230.1 [M+H]⁺. ¹H NMR (400 MHz, CDCl₃) δ ppm 4.62 (s, 2H), 8.06 (d, J = 2.3 Hz, IH), 8.57 (d, J= 2.3 Hz, IH).

References:

WO2010/11316,2010,A1 Location in patent:Page/Page column 67-68