6-Bromo-2-pyridinecarboxaldehyde

Light yellow Flakes

To a 12 L flask equipped with a mechanical stirrer, addition funnel, nitrogen inlet, and thermowell was added BuLi (619 mL, 1.55 mol). To this solution was added dry toluene (750 mL). This solution was cooled to -15° C. in an ice/MeOH bath. To this solution was added BuMgCl (387 mL, 0.774 mol) over 30-45 mins so that the temperature did not exceed 0C during the addition. A fine white to gray suspension formed. This was stirred for 30 mins at -15° C. During this time 2, 6-dibromopyridine (500 g, 2.11 mol) was dissolved in dry toluene (3 L) with some slight external heating. After the stir time the solution of 2, 6-dibromopyridine was charged to an addition funnel and slowly added to the reaction flask at a rate that the temperature did not exceed -5° C. (ca. 1.5 h). Once the addition of the pyridine was complete the mixture was stirred for 45 mins. Then an aliquot was taken and quenched into 20percent aqueous citric acid to determine the extent of metal exchange by In a 250 mL two-necked flask, 0.101 mol of nBuLi (2.5 M hexane solution, 40.4 mL), 80 mL of THF was added, and 2, 6-dibromopyridine (C1, R1=H) (24 g, 0.1) was slowly added dropwise at -78 °C. A solution of mol in 70 mL of THF was maintained at -78 ° C for 2 hours after the addition.N, N-dimethylformamide (11.6 mL, 0.15 mol) was added dropwise, and the mixture was stirred at -78 ° C for 0.5 hour.After returning to 0 ° C, the reaction was quenched by the addition of 70 mL of CH3.To the system, 200 mL of a saturated aqueous solution of NaHCO3 was added, and a white solid was precipitated, which was extracted with CH2Cl2 (200 mL×3), and the organic phase was combined and dried over anhydrous Na2SO4.FiltrationDry, silica gel column chromatography, developing solvent for PE / EtOAc = 20/1, The compound C2 (15.154 g, 81.4 mmol) was obtained as white solid.88.6 ml (0.222 mol) of n-butyllithium (2.5 M in hexane) and 350 ml of THF were placed in a 2 L round-bottom flask, stirred under nitrogen atmosphere at -75 ° C and 2, 6-dibromopyridine 6-dibromopyridine (50.0 g, 0.211 mol) was dissolved in THF (245 mL) and slowly added dropwise at -75 ° C for 1 hour. After 1 hour, stir for another 30 minutes and add 24.5 ml (0.317 mol) of dimethylformamide. Then, the mixture was stirred at a reaction temperature of -40 ° C for 1-1.5 hours and then stirred for 1 hour while slowly raising the temperature to 0 ° C. After the reaction was completed, the reaction mixture was cooled to room temperature, 220 mL of MeOH was added thereto, followed by layer separation with DCM and water. The organic phase was dried over anhydrous MgSO 4 and the organic layer was concentrated and purified by silica gel column chromatography to obtain a white solid compound (Intermediate (4) 17.7 g (yield: 45percent) is obtained.A 2 L round-bottomed flask was charged with 88.6 ml (0.222 mol) of n-butyllithium (2.5 M in hexane)And 350 mL of THF were added thereto. The mixture was stirred under a nitrogen atmosphere at -75 ° C, and 50.0 g (0.211 mol) of 2, 6-dibromopyridine was added.Was dissolved in THF (245 mL)Under -75 was added dropwise slowly for 1 hour.After 1 hour, stir for another 30 minutes and add 24.5 ml (0.317 mol) of dimethylformamide.Then, the mixture was stirred at a reaction temperature of -40 ° C for 1-1.5 hours and then stirred for 1 hour while slowly raising the temperature to 0 ° C.After the reaction was completed, the reaction mixture was cooled to room temperature, 220 mL of MeOH is added and the mixture is then partitioned between DCM and water. The organic phase is dried over anhydrous MgSO4 and the organic layer is concentrated and purified by silica gel column chromatography to obtain 17.7 g (yield: 45percent) of white solid compound (intermediate 10) .A 2 L round-bottom flask was charged with 88.6 ml (0.222 mol) of n-butyllithium (2.5 M in hexane) Add 350 mL of THF and add to -75 ° C The mixture was stirred in a nitrogen atmosphere Dissolve 50.0 g (0.211 mol) of 2, 6-dibromopyridine in 245 mL of THF and slowly drop it at -75 ° C for 1 hour.After 1 hour, stir for another 30 minutes and add 24.5 ml (0.317 mol) of dimethylformamide.Then, the mixture was stirred at a reaction temperature of -40 ° C for 1-1.5 hours and then stirred for 1 hour while slowly raising the temperature to 0 ° C.After the reaction was completed, the reaction mixture was cooled to room temperature, 220 mL of MeOH was added, followed by layer separation with DCM and water, the organic phase was dried over anhydrous MgSO4, The organic layer was concentrated and purified by silica gel column chromatography to obtain 17.7 g (yield: 45percent) of white solid compound (intermediate (4)).To a -10° C. solution of n-BuLi (2.5 M in hexane, 5.6 mL, 14 mmol) in anhydrous toluene (20 mL) was added a solution of n-BuMgCl (2 M in THF, 3.5 mL) over 20 min, maintaining the temperature between -10° C. and 0° C.

A useful synthetic intermediate

Molecular Weight:186.01
XLogP3:1.7
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