Dimethylformamide → HCID 86716087, compound

Temperature

-72 °C

A yellow solution of 6-bromo-2,4-dichloro-8-fluoro-3-phenylquinoline (1.01 g, 2.72 mmol, Intermediate 46, step a) in THF (10 mL) was stirred at −72° C. while n-BuLi (1.15 mL, 2.59 M in hexane, 2.99 mmol) was added dropwise under argon. The resulting homogeneous dark solution was stirred at −72° C. for 20 min, and was then treated with DMF (0.273 mL, 3.53 mmol) dropwise. The homogeneous dark reaction was stirred at −72° C. for 25 min, and was then removed from the cold bath and stirred under ambient conditions for 30 min. The dark homogeneous solution was quenched with 5 M NH4Cl (10 mL) and the aqueous layer was extracted with EtOAc (3×8 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated, and the residue was flash chromatographed with a 20% DCM/heptane to 100% DCM gradient to provide the title compound as a yellow powder.

1. additionwas added dropwise under argon
2. customThe homogeneous dark reaction
3. stirringwas stirred at −72° C. for 25 min
4. customwas then removed from the cold bath
5. stirringstirred under ambient conditions for 30 min
6. customThe dark homogeneous solution was quenched with 5 M NH4Cl (10 mL)
7. extractionthe aqueous layer was extracted with EtOAc (3×8 mL)
8. dry with materialThe combined organic layers were dried (Na2SO4)
9. filtrationfiltered
10. concentrationconcentrated
11. customchromatographed with a 20% DCM/heptane to 100% DCM gradient

ORD record

ord-95862460cfaa4a7caac3b7b049c842f5

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09309222B2