N,N,N',N'-Tetramethylethylenediamine → 2-Pyridinecarboxaldehyde, 3,4-difluoro-

Temperature

-20 °C

Butyllithium (ALDRICH, 1.529 mL, 3.82 mmol) was added dropwise over 10 min at −20° C. (CCl4/acetone) to a solution of N,N,N′,N′-tetramethylethylendiamine (ALDRICH, 0.521 mL, 3.48 mmol) in diethyl ether (anh) (15 mL). Reaction mixture was stirred at −20° C. for 1 h and cooled to −78° C. (acetone/CO2(s)). A solution of 3,4-difluoropyridine (CHEMCOLLECT, 400 mg, 3.48 mmol) in diethyl ether (1 mL) was added dropwise over 15 min at −78° C. Mixture was stirred at −78° C. temperature for 1 hour. N,N-Dimethylformamide (300 μl), previously dissolved in diethyl ether (1 mL), was added dropwise over 10 min at −78° C. Reaction mixture was stirred for 2 hours and was poured carefully onto a rapidly stirring ice/water mixture. Mixture was stirred for 20 min and diluted with ethyl acetate (15 mL). Aqueous layer was further extracted with DCM (4×15 ml). Organic layers were combined, dried over MgSO4(anh) and concentrated. Residue was purified by silica chromatography using Hexane-AcOEt (1:3) as eluents to yield the title compound (148 mg, 1.034 mmol, 30% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm: 10.02-10.03 (m, 1H), 8.63-8.66 (m, 1H), 7.87-7.93 (m, 1H). [ES+MS] m/z 144 (MH+).

1. customReaction mixture
2. stirringMixture was stirred at −78° C. temperature for 1 hour
3. additionwas added dropwise over 10 min at −78° C
4. customReaction mixture
5. stirringwas stirred for 2 hours
6. stirringMixture was stirred for 20 min
7. extractionAqueous layer was further extracted with DCM (4×15 ml)
8. dry with materialdried over MgSO4(anh)
9. concentrationconcentrated
10. customResidue was purified by silica chromatography

ORD record

ord-017900bdee4d453d9c379909d82775da

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09334265B2