Preparation and application background and overview of 2-fluoro-5-bromopyridine
2-Fluoro-5-bromopyridine is an organic intermediate that can be obtained by reacting 2-chloro-5methoxypyridine-bromopyridine with tetramethylammonium fluoride or 2-amino-5-bromopyridine Prepared by diazotization reaction. There are reports in the literature that it can be used to prepare tert-butyl 4-(6-substituted aminopyridin-3-yl)piperidine-1-carboxylate.
Preparation and application of 2-fluoro-5-bromopyridine
Preparation and application report of 2-fluoro-5-bromopyridine 1.
General Procedure E: In a dry oven, combine anhydrous NMe4F (18.6 mg, 0.2 mmol, 2 equiv) and the appropriate aryl chloride or nitroarene substrate (0.1 mmol, 1 equivalent) into a 4 mL vial equipped with a micro stirrer. DMF (0.5 mL) was added, the vial was removed from the dry box and stirred at room temperature for 24 hours unless otherwise stated. The reaction was cooled to room temperature and the internal standard (1,3,5-trifluorobenzene, 100 μL of 0.5 M in toluene) was added. Aliquots were taken for analysis by 19F NMR spectroscopy and GCMS.
Following general procedure E, using 2-chloro-5-bromopyridine (19.1 mg, 0.1 mmol, 1 equiv) afforded 2-fluoro-5-bromopyridine in 100% yield, as obtained from the crude reaction mixture Determined by 19FNMR spectral analysis. 19F NMR spectral data matched that of the real sample (Oakwood Products, s, -71.69 ppm). The identity of the product was further confirmed by GCMS analysis, where a product peak was observed at 6.54 min.
Preparation and application report 2 of 2-fluoro-5-bromopyridine,
Add a solution of 2-amino-5-bromopyridine (1g) in chloroform (20ml) to a solution of sodium nitrofluoroborate (0.745g) in chloroform (10ml) at 0°C. The mixture was stirred at this temperature for 30 minutes, then 1,2-dichlorobenzene (10 ml) was added. Heat the mixture to decompose the chloroform. Continue heating at 150°C for 2 hours. The reaction was cooled, poured on water, and made basic by adding 2N sodium hydroxide. The aqueous phase was extracted into ethyl acetate (3 x 100 ml), the extracts were combined and dried over magnesium sulfate. The dried organic matter was filtered, and the filtrate was concentrated under reduced pressure to obtain an orange oil, which was further purified by silica gel column chromatography to obtain a yellow oil, with a yield of 0.6 g.
Preparation and application of 2-fluoro-5-bromopyridine
CN201711179957.7 discloses a preparation method of 4-(6-substituted aminopyridin-3-yl)piperidine-1-carboxylic acid tert-butyl ester. Using 2-fluoro-5-bromopyridine, N-tert-butoxycarbonyl-4-piperidone, Raney nickel, etc. as raw materials, the target product 4-(6-substituted aminopyridin-3-yl is obtained through a three-step reaction ) piperidine-1-carboxylic acid tert-butyl ester. The process of the present invention is simple and stable to operate, the products in each step are easy to separate, have high yields, are environmentally friendly, and the raw materials are cheap and easy to obtain, which greatly reduces the production costs of existing biological, pharmaceutical, and chemical intermediates, and is conducive to industrial-scale production.
References
[1]FromPCTInt.Appl.,2017024167,09Feb2017
[2]CN201711179957.7 Preparation method of 4-(6-substituted aminopyridin-3-yl)piperidine-1-carboxylic acid tert-butyl ester
[3]FromPCTInt.Appl.,20 pure pyridine 00015614,23Mar2000
