2-Chloro-3-methoxypyridine

White to off-white solid

To a three-necked flask were added 2-chloro-3-hydroxypyridine (5.0 g, 39.0 mmol), N, N- dimethylformamide (60 mL); sodium methoxide (2.30 g, 43.0 mmol ). The reaction was stirred at room temperature for 20 minutes. Methyl iodide (8.20 g, 58.0 mmol) was added to the ice bath and stirred at room temperature for 40 minutes. Water (120 mL) was added and extracted with ethyl acetate (100 mL x 3); the organic phases were combined, washed with water (100 mL x 2) and brine (100 mL), dried over sodium sulphate and filtered. The filtrate was spin-dried to give a yellow liquid, compound 1 (5.58 g, 39.0 mmol, 100percent) which was used directly in the next reaction;Step 1: To a stirred solution of 2-chloro-3-hydroxypyridine (25.4 g, 196 mmol) in dry DMF (250 mL), at 0°C, was added sodium methoxide (11.5 g, 213 mmol). After 5 min, the reaction mixture was allowed to warm to RT. After 1 hour, the mixture was cooled to 0°C and iodomethane (24 mL, 386 mmol) was added. The reaction mixture was stirred at 0°C for 5 minutes, before allowing to warm to RT. After 2 hours, the reaction mixture was concentrated under reduced pressure. The resultant residue was partitioned between diethyl ether and water. The aqueous phase was isolated and extracted twice with diethyl ether. The combined organic extracts were washed with water, brine, dried (Na(a). 2-chloro-3-methoxypyridine To a solution of 2-chloro-pyridin-3-ol (100 g) in DMSO (1 L) was added potassium carbonate (320 g). Methyliodide was added dropwise. The reaction mixture was heated to 50°C overnight. The reaction mixture poured into water and extracted with ethyl acetate. The organic phase was washed with brine, dried over Na(1) Dissolving 10.91 g (0.1 mol) of 3-methoxypyridine in 121.53 g (containing 1.0 mol of hydrogen chloride) of 30.0percent hydrochloric acid, Under stirring, the temperature was controlled at 0-15° C., and 11.83 g of a 25.0percent potassium manganate solution was added dropwise. After the dropwise addition was completed, the reaction temperature was controlled at 0-15° C. to carry out the chlorination reaction of the reaction system.During the reaction, samples were taken at regular intervals and detected with high performance liquid chromatography.When it was detected that the mass of 2-chloro-3-methoxypyridine in the reaction system accounted for 80.5percent of the total mass of organic substances in the reaction system, The reaction was terminated by adding 11.36 g (0.06 mol) of stannous chloride to obtain a feed solution containing 2-chloro-3-methoxypyridine; (2) 71.8 g of methylene chloride was added to the reaction mixture, and the mixture was stirred and extracted for 2 hours. The mixture was allowed to stand for 1 hour and the organic phase was taken and allowed to cool down to -15°C to -5°C.The solids were extracted and analyzed from the organic phase. The resulting 10.20 g of solid was 2-chloro-3-methoxypyridine. The yield was calculated to be 71percent. After the determination, the main content was 98.0percent.

Molecular Weight:143.57
XLogP3:1.2
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:143.0137915
Monoisotopic Mass:143.0137915
Topological Polar Surface Area:22.1
Heavy Atom Count:9
Complexity:89.1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes