(5-CHLORO-2-METHOXYPYRIDIN-4-YL)BORONIC ACID

General procedure: General Method 1A: Preparation of a boronic acid At-78C, LDA (2 molar in THF/heptane/ethylbenzene) was added to a solution of theappropriate pyridine derivative in THF (3 ml/mmol), the mixture was stirred for2-4 h and triisopropyl borate was then added quickly. The reaction mixture wasmaintained at -78 C for a further 2-3 h and then slowly thawed to RT overnight.After addition of water, the THF was removed under reduced pressure and theaqueous phase was extracted twice with ethyl acetate The aqueous phase wasacidified with 2M hydrochloric acid, generally resulting in formation of aprecipitate which was filtered off, washed with water and dried. The aqueousphase was extracted three times with ethyl acetate. The combined organic phaseswere dried (sodium sulphate), filtered and concentrated under reduced pressure.10.0 g (69.65 mmol) of 5-chloro-2-methoxypyridine werereacted according to General Method 1A.The desired product precipitated on acidification with hydrochloric acid (2N).Yield: 10.44 g (purity 91percent, 73percent of theory)Under a nitrogen atmosphere, 300 g of anhydrous tetrahydrofuran was added to the reaction flask, stirring was continued, 17 g of 5-chloro-2-methoxypyridine was added and cooled to -30C.A solution of 70 mL of 2.0 M of n-BuLi was slowly added dropwise, and after stirring for 30 minutes, 1, 3 g of 1, 4, 7, 10-tetramethyl-1, 4, 7, 10-tetraazacyclododecane was slowly added dropwise.After 2 hours of incubation, 41 mL of triisopropyl borate was slowly added dropwise at -30 ° C, stirred for 1 hr, slowly raised to room temperature and stirred for 1 hour.And 400 g of concentrated hydrochloric acid was added thereto, followed by stirring for 1 hour to carry out a hydrolysis reaction.The layers were allowed to stand, and the organic layer was washed three times with water (3 x 100 g).The aqueous layers were combined and the aqueous layer was extracted once with 100 ml of petroleum ether. The combined organic layers were dried over 50 g of anhydrous sodium sulfate and filtered.The filtrate was concentrated to dryness to give 6-chloro-2-methoxy-4-pyridine boronic acid 16 g, Under a nitrogen atmosphere, 300 g of anhydrous tetrahydrofuran was added to the reaction flask, stirring was continued, 17 g of 5-chloro-2-methoxypyridine was added and cooled to -30C.Sulfur was added dropwise to 70 mL of 2.0 M of n-BuLi. After stirring for 30 minutes, 26 g of 1, 4, 7-trimethyl-1, 4, 7-triazacyclononane was slowly added dropwise.After incubation for 2 hours, 26 mL of trimethyl borate was slowly added dropwise at -30 ° C, stirred for 1 hr, slowly rose to room temperature and stirred for 1 hour.And 400 g of concentrated hydrochloric acid was added thereto, followed by stirring for 1 hour to carry out a hydrolysis reaction.The layers were allowed to stand, and the organic layer was washed three times with water (3 x 100 g).The aqueous layers were combined and the aqueous layer was extracted once with 100 ml of petroleum ether. The combined organic layers were dried over 50 g of anhydrous sodium sulfate and filtered.The filtrate was concentrated to dryness to give 16 g of product 5-chloro-2-methoxy-4-pyridine boronic acid.

Molecular Weight:187.39
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:187.0207509
Monoisotopic Mass:187.0207509
Topological Polar Surface Area:62.6
Heavy Atom Count:12
Complexity:149
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes