Preparation of 5-chloro-2-methoxypyridine-4-carbaldehyde_Industrial additives

Preparation background and overview of 5-chloro-2-methoxypyridine-4-carbaldehyde

5-Chloro-2-methoxypyridine-4-carbaldehyde can be used as a pharmaceutical synthesis intermediate and an organic synthesis intermediate. It is mainly used in laboratory research and development processes and chemical and pharmaceutical synthesis processes. If 5-chloro-2-methoxypyridine-4-carbaldehyde is inhaled, move the patient to fresh air; if skin contact occurs, remove contaminated clothing and rinse skin thoroughly with soap and water. If discomfort occurs , seek medical attention; if eye contact occurs, separate eyelids, rinse with running water or saline, and seek medical attention immediately; if ingested, rinse mouth immediately, do not induce vomiting, and seek medical attention immediately.

Preparation of 5-chloro-2-methoxypyridine-4-carbaldehyde

5-Chloro-2-methoxypyridine-4-carbaldehyde was prepared as follows: 5-chloro-2-methoxypyridine-4-methylpyridine (20mmol) was dissolved in N,N-dimethylformamide (38mL ) was added to the solution in tert-butoxybis(dimethylamino)methane (7.0 mL, 33.9 mmol). The reaction mixture was heated at 120°C for 2 hours. The cooled reaction mixture was concentrated in vacuo to give a thick orange oil, which was redissolved in tetrahydrofuran (40 mL) and poured slowly into a slurry of sodium periodate in water (150 mL) at 0°C. separate flask. The reaction flask was equipped with an overhead stirrer and allowed to warm to room temperature. The reaction mixture was mixed vigorously for three hours and then diluted with dichloromethane (150 mL) and filtered.

The collected solid was washed with dichloromethane (2×150 mL), and the organic layer was separated from the filtrate and washed with saturated sodium bicarbonate solution (50 mL). The aqueous layer was neutralized by adding solid sodium bicarbonate and then back-extracted with dichloromethane (100 mL). The organic portions were combined, dried over sodium sulfate, filtered, and evaporated in vacuo to give a residue which was purified by flash chromatography (silica, 120 g, ISCO, 0-40 in heptane % ethyl acetate) to give dimethyl sulfoxide the title compound as 5-chloro-2-methoxypyridine-4-carbaldehyde as nickel fluoroborate yellow solid.