2-Methylquinoline → Diethyl 2-quinolinylmethylphosphonate

Temperature

-45 °C

To a solution of diisopropylamine (15 g, 150 mmol) in THF (250 mL) was added n-BuLi (2.5 M in hexane, 59 mL, 150 mmol) at −78° C. under a nitrogen atmosphere. The resulting solution was stirred at −45° C. for 0.5 h, then cooled to −78° C., and 2-methylquinoline (10 g, 70 mmol) was added. The resulting solution was stirred at −78° C. for 0.5 h and then diethyl chlorophosphonate (14 g, 80 mmol) was added. The reaction mixture was stirred at −78° C. for 1 h and then at rt for 1 h. The reaction mixture was treated with saturated NH4Cl (300 mL) and extracted with EtOAc (3×350 mL). The organic layers were combined, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue obtained was purified by flash column chromatography on silica gel (EtOAc/petroleum ether (1:2 v/v)) to obtain compound 58a as a yellow oil. Mass Spectrum (LCMS, ESI pos.) Calcd. For C14H18NO3P: 280.1 (M+H). Found 280.2.

1. temperaturecooled to −78° C.
2. stirringThe resulting solution was stirred at −78° C. for 0.5 h
3. stirringThe reaction mixture was stirred at −78° C. for 1 h
4. waitat rt for 1 h
5. extractionextracted with EtOAc (3×350 mL)
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customThe residue obtained
10. customwas purified by flash column chromatography on silica gel (EtOAc/petroleum ether (1:2 v/v))

ORD record

ord-52e98c3df02140578998a6a31f1f9004

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09193736B2