2-Chloro-4-iodopyridine-3-carboxaldehyde

Yellow-green solid

Step 1 :2-Chloro-4-iodonicotinaldehydeA mixture of 2-chloro-3-iodopyridine (5.0 g, 21 mmol) in dry THF (30 mL) was slowly added to a cold (-78 °C) solution of lithium diisopropylamide (15 mL, 30 mmol) in dry THF (50 mL). The resulting mixture was stirred for 3 h at this temperature. Ethyl formate (4.0 g, 54 mmol) was then added. Stirring was continued for 1.5 h at the same temperature. Water (10 mL) was added to quench the reaction, and then the resulting mixture was warmed to room temperature. 2M HC1 (50 mL) was added and then the THF was removed under reduced pressure. The aqueous residue was extracted with ethyl acetate (2 x 50 mL). The combined organic extracts were washed with brine, dried over NaA mixture of 2-chloro-3-iodopyridine(5.0g, 21mmol) in dry THF (30 mL) was slowly added to a cold (-78°C) solution oflithiumdiisopropylamide(15 mL, 30mmol) in dry THF (50 mL). The resulting mixture was stirred for 3h at this temperature.Ethylformate(4.0g, 54mmol) wasthenadded.Stirring continued for 1.5 h at the same temperature.Water (10 mL) was added to quench the reaction, and then theresultingmixture was warmed toroom temperature.2 MHCl(50 mL) was added and then the THF was removed under reduced pressure.The aqueous residue was extracted withethyl acetate(2 x 50 mL).The combined organic extracts were washed with brine, dried over NaAccording to the literature, 17 a dry, argon-flushed Schlenk flask equipped with a magnetic stirring bar and a septum was charged with a solution of LDA (18.0 mmol, 1.0 M in THF) and cooled to –78 °C. 2-Chloro-3-iodopyridine (3.1 g, 13.0 mmol) was added dropwise tothe cooled solution. The resulting mixture was stirred for 3 h at –78 °C. Ethyl formate (2.5 g, 34.0 mmol) was then added and stirred for 1.5 hat –78 °C. The resulting solution was quenched with sat. aq NH4Cl (80 mL), extracted with EtOAc (3 × 120 mL), and the combined organic phases were dried (anhyd MgSO4). After filtration, the solvents were evaporated in vacuo. The crude product was purified by flash column chromatography on silica gel (i-hexane/EtOAc, 9:1 to 8:2 +Et3N 2percent) yielding 2-chloro-4-iodonicotinaldehyde as a yellow solid(1.8 g, 52percent). 1H NMR (400 MHz, CDCl3): δ = 10.19 (s, 1 H), 8.07 (d, J = 5.1 Hz, 1 H), 7.94 (d, J = 5.1 Hz, 1 H).

Molecular Weight:267.45
XLogP3:1.9
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:266.89479
Monoisotopic Mass:266.89479
Topological Polar Surface Area:30
Heavy Atom Count:10
Complexity:133
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes