2,6-Difluoropyridine-3-boronic acid

L2 was synthesized according to literature procedures [S1, S2] with some modifications. In around-bottomed flask, lithium diisopropylamide (LDA) solution was prepared as follows: THF (20mL) solution of diisopropylamine (3.4 mL) was slowly added n-butyl lithium (1.67 M in n-hexane, 24 mmol, 14 mL) at 0 C, then was stirred at the same temperature for 20 min. In anotherround-bottomed flask, THF (20 mL) solution of 2, 6-difluoropyridine (20 mmol, 1.8 mL) was stirredat −78 C and was added LDA solution prepared above via a cannula. After stirring at −78 C for 30min, the reaction mixture was added THF (10 mL) solution of trimethyl borate (24 mmol, 2.5 g, 2.7mL), then warmed to ambient temperature over 1 h. The reaction was quenched by adding 2Maqueous sodium hydroxide (40 mL). Separated aqueous layer was neutralized (pH 8) by adding 4Mhydrochloric acid and extracted with ethyl acetate (organic layer A). Re-adding 4M hydrochloricacid to the aqueous layer to pH 6.5 afforded insoluble organic materials. Repeated extraction withethyl acetate for three times gave organic layer B. Re-adding 4M hydrochloric acid to the aqueouslayer to pH 4 followed by repeated extraction with ethyl acetate for three times gave organic layer C.The combined organic layer (B and C) was dried over anhydrous sodium sulfate, and concentrated invacuo. 2, 6-difluoropyridine-3-boronic acid was obtained in 94percent yield (3.0 g, 19 mmol) as theresidue. This compound was used for the next step without further purification.Under a nitrogen atmosphere, 7.5 mL (12 mmol) of 1.6 M lithium diisopropylamine and 0.91 mL (10 mmol) of 2, 6-difluoropyridine were added to 40 mL of tetrahydrofuran, and kept reacting at -78°C for 1 h. (1) Synthesis of 2, 6-difluoro-pyridyl-3-boronic acid Under a nitrogen atmosphere, 7.5 mL (12 mmol) of 1.6 M lithium diisopropylamine and 0.91 mL (10 mmol) of 2, 6-difluoropyridine were added to 40 mL of tetrahydrofuran, and kept reacting at -78° C. for 1 h. After the addition of 1.40 mL (12.5 mmol) of trimethyl borate, the temperature was naturally warmed to room temperature and the mixture was kept mixing to react for 1 h. The reaction mixture was quenched by slowly adding 20 mL of an aqueous solution of 5 wt percent NaOH, after stirring for 10 min, an aqueous solution of 3N HCl was added dropwisely to adjust the pH to neutral. The mixture was extracted several times with ethyl acetate and the organic phases were combined, solvent was removed by rotary evaporation to give 1.43 g of white solid in 90percent yield. Under the protection of nitrogen, 7.5 ml (12mmol) 1.6M lithium diisopropylamine of slow instillment to -78 ° C THF solution containing 0.91 ml (10mmol) 2, 6-difluoropyridine and 40 ml ethyl ether of the mixed solution, keep -78 ° C temperature stirring reaction 1h. To be the reaction system by adding 1.40 ml (12.5mmol) after three methyl ester borate, natural temperature raising to room temperature, to continue stirring reaction 1h. Reaction mixed solution is slowly added 20 ml of the mass fraction of 5percent aqueous solution of NaOH of termination reaction, stirring 10 min later, by adding proper dropwise 3N adjusting the pH value of the aqueous solution of HCl to neutral. Ethyl acetate extraction many times, combined with the phase, rotary evaporate the solvent, get white solid 1.43g, the yield is 90percent.Under an argon atmosphere, in a 500 ml, three-neck flask, 5.00 g of

Molecular Weight:158.90
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:1
Exact Mass:159.0303149
Monoisotopic Mass:159.0303149
Topological Polar Surface Area:53.4
Heavy Atom Count:11
Complexity:138
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes