5-Bromo-3-pyridinecarboxaldehyde

Take 3, 5-dibromopyridine 250g, tetrahydrofuran 1000ml, tetramethylethylenediamine 150g, into a 5L reaction flask, Turn on stirring. The system ice water bath was cooled to 10-15°C. Take isopropylmagnesium chloride (2.6M, THF) 750ml, Drip into the reaction solution and keep it below 15°C (slightly warming). After dropping, remove the ice bath.Maintain 1-2h at 20-25°C. The reaction solution was cooled in an ice water bath to 5-10°C.DMF 130g was taken and dissolved in 100 ml THF. The DMF-THF mixture was slowly added dropwise into the reaction solution.Keep the internal temperature below 15°C (exotherm should be added slowly).After the completion of the drop, maintain the reaction at 10-15°C for 30 minutes.The reaction solution was poured into 2L ice water, stirred for 10 minutes, and allowed to stand and separate, collecting the aqueous phase and the organic phase, respectively.The aqueous phase was extracted once with 1 L of ethyl acetate and the organic phases were combined. The organic phase was washed successively with 1 L of water, 1 L of saturated saline, and dried over anhydrous sodium sulfate.Distillation under reduced pressure at 50-55°C yields a greyish brown crude product. To the crude product was added PE:EA=6:1 (W:W) mixed solvent 200 ml and beaten at 20-25°C for 1 h. Filter and filter cake to rinse once with 50ml PE. The infrared lamp was dried to give an off-white solid to white solid, 112 g, yield 67.3percent.In diethyl ether (42.0 mL) was dissolved 3, 5-dibromopyridine (1.00 g, 4.22 mmol). n-Butyllithium (2.76 mol/L solution in n-hexane, 1.61 mL, 4.43 mmol) was added dropwise at −78° C., and the mixture was stirred at the same temperature for 30 minutes. Further, DMF (0.98 mL, 12.7 mmol) was added and the mixture was stirred for 3 hours allowing the temperature to rise slowly to room temperature. A saturated aqueous ammonium chloride solution and water were added to the reaction mixture. Extraction with ethyl acetate, washing with saturated brine and drying over anhydrous sodium sulfate were performed. After filtration, the solvent in the filtrate was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate 7/3) to give 5-bromonicotinaldehyde (314 mg, 40percent).(5-Bromo-pyridin-3-yl)-methanol (1.13 g, 6.00 mmol) was dissolved in CHCI4.5 g (21 mmol) of pyridinium chlorochromate are added at room temperature to a solution of 3 g (16 mmol) of (5-bromopyrid-3-yl) methanol in 70 ml of dichloromethane. After stirring for 1 hour, 70 ml of diethyl ether are added and the reaction medium is again stirred for 1 hour. The precipitate is filtered off through sodium sulfate and the filtrate is evaporated to dryness. The residue obtained is purified by chromatography on a column of silica eluted with a 7/3 heptane/ethyl acetate mixture. 1 g (35percent) of 5-bromopyridine-3-carbaldehyde is obtained.5-Bromo-3-pyridinecarboxaldehyde (XXXVII) WORKING EXAMPLE 6

Molecular Weight:186.01
XLogP3:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:184.94763
Monoisotopic Mass:184.94763
Topological Polar Surface Area:30
Heavy Atom Count:9
Complexity:107
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes