Preparation background and overview of 2-fluoro-5-nitrophenylboronic acid pinacol ester
2-Fluoro-5-nitrobenzene borate pinacol ester is an organic intermediate, which can be obtained by the reaction of 2-bromo-1-fluoro-4-nitrobenzene and diboron acid pinacol ester. It can be used for Perform Suzuki reaction.
[Zinc Pyrithione Label: Title] Preparation
Preparation Report 1 of 2-Fluoro-5-nitrobenzeneboronic acid pinacol ester,
Place 2-bromo-1-fluoro-4-nitrobenzene (13.2g, 60mmol), 4,4,4′,4′,5,5,5′,5′-octamethyl-2, 2′-bis(1,3,2-dioxaboropentane) (22.8g, 90mmol), [1,1′-bis(diphenylphosphino)ferrocene]palladium dichloride (880mg, 12mmol) ), potassium acetate (17.6g, 180mmol) was dissolved in 1,4-dioxane (180mL), replaced with nitrogen, heated to 90°C and stirred overnight. LC/MS detected that the reaction was complete. Water (150mL) was added to the reaction solution, extracted with ethyl acetate (200mL), the organic phase was washed with saturated brine (150mL*2), dried over anhydrous sodium sulfate, concentrated and purified using silica gel preparative chromatography (petroleum ether) : Ethyl acetate = 10:1) to obtain 2-fluoro-5-nitrophenylboronic acid pinacol ester (14.0 g basic magnesium carbonate, yield 87.3%). 1HNMR(MHz,DMSO-d6)δ:8.44-8.39(m,2H),7.49-7.45(m,1H),1.34(s,12H).
Preparation Report 2 of 2-Fluoro-5-nitrobenzeneboronic acid pinacol ester,
Use 2-bromo-1-fluoro-4-nitrobenzene (66g, 300mmol), potassium acetate (58.9g, 600mmol), bis(pinacolyl)diboron (83.8g, 330mmol) and dichloro [1,1′-bis(diphenylphosphino)ferrocene]-palladium(II) dichloromethane adduct (7.35 g, 9 mmol) in 1,4-dioxane (900 ml, containing 18 ml dichloromethane) The resulting mixture (methyl sulfoxide) was degassed with nitrogen for 1 hour and then heated at 90°C for 14 hours. The reaction was cooled to room temperature and concentrated in vacuo. The residue was stirred with 2N sodium hydroxide (11) for 10 minutes and then filtered. The filtrate was extracted with diethyl ether (2×750ml), and the organic matter was discarded. The aqueous component was cooled to 0°C, and then 36% hydrochloric acid (approximately 175 ml) was added dropwise within 15 minutes for treatment until pH 5 was reached. The resulting precipitate was left at 0°C for 2 hours, then filtered and washed with ice-cold water. The obtained sand-colored solid was dried with phosphorus pentoxide under vacuum (300mmHg) to obtain 2-fluoro-5-nitrobenzene borate pinacol ester (76.1g, 95%): δH (MHz, CDCl3 ) 1.38 (12H, s), 7.17 (1H, dd, J9 and 9), 8.32 (1H, ddd, J9, 5 and 3), 8.64 (1H, dd, J5 and 3).
References
[1][Chinese invention] CN201910042996.5 Pyridine N-oxide derivatives and their preparation methods and applications
[2] [Invented in China, authorized by China] CN02807057.7 Imidazo-pyrimidine derivatives as GABA receptor ligands
