Dimethylformamide → 4-Chloropyridine-3-carbaldehyde

Temperature

-78 °C

To a solution of diisopropylamine (18.2 mL, 0.13 mol) in THF (200 mL, 0.5 M) at −78° C. was added n-butyl lithium (2.5 M in hexane, 52 mL, 0.13 mol) dropwise. After 30 min, 4-chloropyridine from Step A in THF (10 mL) was added and the reaction mixture was stirred at −78° C. for 1 h. To the resulting reddish-brown solution at −78° C. was added N,N-dimethylformamide (12.4 mL, 0.16 mol). The reaction mixture was allowed to warm slowly to room temperature over a 15 h period, and then the reaction was quenched with water (150 mL). The THF was removed in vacuo and the aqueous layer was extracted with isopropyl acetate (3×150 mL). The organic layers were combined, dried over sodium sulfate, filtered and the solvent was removed in vacuo to give the crude product as a brown oil. This residue was purified by silica gel chromatography (using 5% EtOH in EtOAc) to afford 3.97 g of the title intermediate as a yellow solid (Rf=0.6, 28% yield).

1. temperatureto warm slowly to room temperature over a 15 h period
2. customthe reaction was quenched with water (150 mL)
3. customThe THF was removed in vacuo
4. extractionthe aqueous layer was extracted with isopropyl acetate (3×150 mL)
5. dry with materialdried over sodium sulfate
6. filtrationfiltered
7. customthe solvent was removed in vacuo
8. customto give the crude product as a brown oil
9. customThis residue was purified by silica gel chromatography (using 5% EtOH in EtOAc)

ORD record

ord-918c1c9e8ff547d4a6c3142a896b403b

Source dataset

uspto-grants-2007_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07285564B2