2-Chloropyridine-5-carbaldehyde

Off-white crystal

According to a procedure of Lee et al. [22] oxalylchloride (3.81 g, 30.0 mmol, 3.0 eq) was dissolved in CH2Cl2 (35 mL) at -78C (dry ice/acetone). Then DMSO (46.9 g, 0.60 mol, 60.0 eq.)was added dropwise under stirring and the reaction mixture was stirred for additional 30 min at -78C. Then 2-chloro-5-(hydroxymethyl)pyridine (1.44 g, 10.0 mmol, 1.00 eq) was dissolved in CH2Cl2(10 mL) and added dropwise with a syringe to the cold reaction mixture. Afterwards, the reaction mixture was stirred for 40 min at -78C and NEt3 (91.9 g, 0.90 mol, 90.0 eq) was added to the reaction mixture at a rate of 2.0 mL/min. The reaction mixture was stirred for 1 h at -78C, followed by another 1.5 h stirring at r.t. The reaction mixture was then diluted with Et2O (60 mL) and the organic phase was washed successively withNaHCO3(sat., aq., 2 × 30 mL), KHSO4(1 M, aq., 60 mL) and NaHCO3(sat., aq., 30 mL). After phase separation the organic phase was dried over Na2SO4, the solid removed by filtration and the solvent was removed in vacuum. Further cleaning with liquid chromatography(LC) (SiO2, n-pentane/EtOAc/NEt3= 200/100/6) gave the desired product as yellowish solid (1.35 g, 96percent).General procedure: To a mixture of alcohol in dry DMSO (10 volume) was added 1 equiv of polymer bromide and the reaction mixture was stirred at room temperature for a given period of time (Table 1). After the completion of the reaction, the reaction mixture was filtered and the polymer bed washed with DMSO. Combined DMSO layers were quenched with ice-water mixture and extracted with ether. The ether layer was given water wash, brine wash, dried over anhydrous sodium sulphate, and concentrated to get the pure carbonyl compounds. All the products were characterized by NMR and MS analysis.To a solution of the alcohol from above (481 mg, 3.35 mmol) in CHClGeneral procedure: DBDMH (1 mmol) was added to a mixture of 1b (1 mmol) and dichloromethane (20ml). The reaction was kept at room temperature. After the mixture was stirred for0.5h, the mixture was washed with water (330 ml), dried with anhydrous MgSO4, filtered, and vacuum evaporated. The residue was purified by column chromatography (silica gel: petroleum ether/ethyl acetate, 30:1) to afford the product as light yellowsolid (93percent yield).To a solution of PCC (58 g, 0.27 mol) in DCM (1500 ml) was added the product of the proceeding step (26 g, 0.184mol) as a solution in DCM drop wise at 0°C. The mixture was then stirred for 2h at 20°C. It was filtered through diatomaceous earth and the filter contents were washed with DCM. The organic phase was concentrated to give the crude product, which was purified by column chromatography to give the product (15 g, yield: 60.1 percent). 1H NMR (400 MHz, CDCI3): δ 10.067 (s, 1 H), 8.874 (s, 1 H, J=3Hz), 8.158-8.138 (d, 1 H, J=8Hz), 7.534-7.513 (d, 1 H, J=8Hz)5-Bromo-2-chloropyridine (T-9) (15.0 g) and diethyl ether (450 ml) were put in a reaction vessel and cooled to -50 °C under an atmosphere of nitrogen. n-Butyllithium (1.57 M in n-hexane; 54.6 ml) was added dropwise in the temperature range of -50 °C to -45 °C, and the stirring was continued for another 90 minutes. After the reaction vessel had been cooled to -70 °C, formylpiperidine (9.70 g) was added dropwise in the temperature range of -70 °C to -65 °C, and the stirring was continued for another 60 minutes while the mixture was allowed to return to room temperature. The resulting reaction mixture was poured into ice-water (500 ml) and mixed with it. Diethyl ether (200 ml) was added to the solution to separate organic and aqueous phases, and extraction was carried out. The combined organic phase was washed with water and dried over anhydrous magnesium sulfate. The resulting solution was concentrated under reduced pressure and the residue was purified with a fractional operation by means of column chromatography (silica gel; toluene). The product was further purified by recrystallization from heptane. The solvent was distilled off and the product was dried, giving 2-chloro-5-formylpyridine (T-10) (7.01 g). The yield based on the compound (T-9) was 68percent.Take 50g of raw material 2-chloro-5-chloromethyl pyridine, Soluble in 100g DMSO and 200g tolueneAdd 48g of sodium dihydrogen phosphate, 3g of potassium bromide. Stirring, Nitrogen was bubbled under the liquid surface.Warm up to 90100°C reaction.After the reaction was completed, it was briefly distilled under reduced pressure and purified by distillation. The distillate was added with 50 g of water and 100 g of methyl tert-butyl ether (MTBE). The mixture was washed and separated, and the MTBE was recovered from the organic phase to obtain 2-chloro-5-aldehyde pyridine, which was weighed 35.6 g and the molar yield was about 81percent.

Molecular Weight:141.55
XLogP3:1.2
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:140.9981414
Monoisotopic Mass:140.9981414
Topological Polar Surface Area:30
Heavy Atom Count:9
Complexity:107
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes