5-Bromo-3-(difluoromethyl)-2-methoxypyridine synthesis

Yield: 100%

Reaction Conditions:

with diethylamino-sulfur trifluoride in dichloromethane at 0 - 25; for 72 h;Inert atmosphere;

Steps:

22i 5-Bromo-3-(difluoromethyl)-2-methoxypyridine
Example 22i 5-Bromo-3-(difluoromethyl)-2-methoxypyridine To 5-bromo-2-methoxynicotinaldehyde (5 g, 23 mmol) in dry CH₂Cl₂ (100 mL) at 0° C. under argon was diethylaminosulphur trifluoride (3.69 mL, 30.1 mmol) added over 1 min. The reaction mixture was stirred for three days while the reaction warmed to r.t. The reaction was quenched by the addition of sat. aqueous sodium bicarbonate solution. The reaction mixture was combined with another reaction based on 5-bromo-2-methoxynicotinaldehyde (100 mg, 0.46 mmol) prior to workup. The phases were separated and the water phase was further extracted with CH₂Cl₂ (x 3). The organic layers were pooled, dried (Na₂SO₄), filtered and concentrated to give the title compound (5.71 g, quant. yield): ¹H NMR (400 MHz, DMSO-d₆) δ ppm 3.94 (s, 3H), 7.04 (t, 1 H), 8.10-8.16 (m, 1H), 8.48 (m, 1H); MS (ES+) m/z 238 [M+H]⁺.

References:

ASTRAZENECA AB US2012/165346, 2012, A1 Location in patent:Page/Page column 18