With the rapid development and complex challenges of chemical substances, the synthesis of new drugs is usually one of the most effective ways to increase yield.886365-46-4, name is 5-Chloro-3-methylpyridine-2-carboxylic acid, molecular formula is C7H6ClNO2, molecular weight is 171.58, as common compound, the synthetic route is as follows.HPLC of Formula: C7H6ClNO2
A 100 L r.b. flask was flushed with nitrogen, fitted with thermocouple, overhead stir paddle, and dropping funnel. The flask was charged with a 3M solution of methylmagnesium chloride and stirring begun. The flask was packed in an ice bath. When the temperature reached 5 C., a solution of chloro-ester was added by dropping funnel. The rate of addition was controlled to keep temperature below 30 C., and generally between 20-25 C. After addition was complete, the reaction was aged for 30-45 minutes longer and assayed. The reaction was quenched by addition of ethyl acetate 800 mL followed by methanol 800 mL, again not allowing temperature to rise above 30 C. pH was adjusted with 2N hydrochloric acid solution to pH=4. The acidic reaction solution was extracted with ethyl acetate 9 L. The organic layer was extracted once with 1N hydrochloric acid solution 40 L, and again with 1N hydrochloric acid solution 20 L. The combined aqueous layers were adjusted with 10 N sodium hydroxide to pH=8 (4 L) (Note: an oily layer was noted to separate out on top). The basic aqueous layer was extracted once with ethyl acetate 10 L, dried and concentrated to a solution of 200 mg/mL concentration of product. An aliquot of product solution was concentrated to an oil and purified further by column chromatography on a silica gel 5-10% ethyl acetate in hexanes gradient for characterization purposes. NMR 1H delta: 1.53 (s, 6H), 4.44 (br s, 1H), 7.35 (dd, J=8.4, 0.7 Hz, 1H), 7.66 (dd, J=8.4, 2.4 Hz, 1H), 8.46 (dd, J=2.3, 0.6 Hz, 1H). NMR 13C delta: 30.5, 71.9, 119.5, 130.1, 136.6, 146.4, 164.4.
At the same time, in my other blogs, there are other synthetic methods of this type of compound,886365-46-4, 5-Chloro-3-methylpyridine-2-carboxylic acid, and friends who are interested can also refer to it.
Reference:
Patent; Albaneze-Walker, Jennifer; Ceglia, Scott; Murry, Jerry Anthony; Soheili, Arash; US2004/102472; (2004); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem