2,4-Dichloropyridine-3-carboxaldehyde

To a solution of 2, 4-dichloropyridine (2 g, 13.51 mmol) in tetrahydrofuran (20 mL) at -78° C., was added LDA, 2M in THF/heptane/ethylbenzene (8.11 mL, 16.22 mmol) and the solution was stirred for 30 min. DMF (10.46 mL, 135 mmol) was added and the solution was stirred for 1 h and then warmed RT. To a solution of 2, 4-dichioropyridine (2 g, 13.51 mmol) in tetrahydrofuran (20 mL) at -78 °C, was added LDA, 2M in THF/heptane/ethylbenzene (8.11 mL, 16.22 mmol) and the solution was stirred for 30 mm. DMF (10.46 mL, 135 mmol) was added and the solution was stirred for 1 h and then warmed RT. The reaction mixture was quenched with saturated NH4C1 solution and diluted with ethyl acetate (50 mL). The organic layer was washed with saturated NaHCO3 (2X10 mL), water (20 mL), dried over Na2SO4 and concentrated under reduced pressureto afford 2, 4-dichloronicotinaldehyde (2 g, 11.36 mmol, 84percent yield) as a yellow solid. ‘H NMR (400 MHz, CDC13) ö 10.49 (s, 1H), ), 8.44 (d, J = 5.4 Hz, 1H), 7.43 (d, J = 5.4 Hz, 1H).Intermediate 12, 4-Dichloro-pyridine-3-carbaldehydeTo a solution of n-butyllithium (1.6 M in hexane, 64 ml, 101 mmol) in THF (150 ml) at -78 °C was added diisopropylamine (14.3 ml, 101 mmol) dropwise. The reaction mixture was allowed to warm to 0 °C over 1 h, and then cooled down to -78 °C. 2, 4-Dichloropyridine (11 ml, 101 mmol) was added dropwise and the solution was stirred at -78 °C for 2.5 h. N-Formylpiperidine (11.2 ml, 101 mmol) was then added dropwise and the mixture stirred at -78 °C for a further 1.5 h. The solution was quenched at -78 °C with saturated NHIntermediate 10A) 2, 4-dichloropyridine-3-carbaldehyde [1031] To a solution of 2, 4-dichloropyridine (10 g) in THF (100 mL) was added dropwise lithium diisopropylamide solution (2M, 37 mL) at -78°C. The reaction mixture was stirred at -78°C for 1 hr. To the reaction mixture was added dropwise 1-formylpiperidine (7.7 g) at -78°C. The reaction mixture was stirred at -78°C for 2 hr. The reaction mixture was added to 10percent aqueous acetic acid solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium hydrogencarbonate solution and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/petroleum ether) to give the title compound (7.0 g). 28a) To a stuffed solution of THF (200 mL) was added n-BuLi (i.6M in hexane, 46.4 mL, 74.32 mmol) dropwise at -78 °C. Then, DIPEA (11.3 mL, 81.08 mmol) was added to the reaction mixture slowly at -78 °C and the temperature of the reaction mixture was gradually raised to 0 °C over a period of 1 h. Then 2, 4-dichloropyridine (10 g, 67.57 mmol) dissolved in THF (30 mL) was slowly added to the reaction mixture at -78 °C and the reaction mixture was allowed to stir at same temperature for ih. Then, ethyl formate (10.91 mL, 135.14 mmol) dissolved in THF (20 mL) was slowly added to the reaction mixture at -78 °C and the resultant reaction mixture was stirred at -78 °C for 45 mm. The reaction was monitored by TLC. After completion of reaction, the reaction mixture was quenched using saturated NH4C1 solution (50 mL) at 0 °C slowly. The aq. layer was then extracted with EtOAc (2x300 mL). The combined organic layers were washed with water (400 mL), brine (100 mL), dried over Na2SO4 and concentrated to afford 2, 4—dichioronicotinaldehyde (8.5 g) as a brown solid, which was used for next- step without any further purification.

Molecular Weight:176.00
XLogP3:1.9
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:174.9591691
Monoisotopic Mass:174.9591691
Topological Polar Surface Area:30
Heavy Atom Count:10
Complexity:131
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes