Tert-butyl 2-methylpropanoate → Tert-butyl 2-(9-bromo-1-chlorobenzo[c]-1,6-naphthyridin-6-yl)-2-methylpropanoate

To a stirred suspension of 9-bromo-1,6-dichlorobenzo[c]-1,6-naphthyridine (5 g, 15.24 mmol) in Toluene (50 ml) was added tert-butyl 2-methylpropanoate (2.64 g, 18.29 mmol). The reaction mixture was cooled to 0° C. A solution of NaHMDS (1M in THF, 3.35 g, 18.29 mmol) was added dropwise, and the reaction mixture was allowed to warm to room temperature. After 5 hours, the reaction was quenched with aqueous saturated ammonium chloride (50 mL), and extracted with EtOAc (1×100 mL). The organic layer was dried over sodium sulfate, filtered and concentrated. The residue was adsorbed on to silica gel and purified by column chromatography on silica gel, eluting with an EtOAc/Hexanes gradient to afford tert-butyl 2-(9-bromo-1-chlorobenzo[c]-1,6-naphthyridin-6-yl)-2-methylpropanoate. LRMS (ESI) calc'd for (C20H20BrClN2O2) [M+H]+, 437.0; found 437.0.

1. temperatureto warm to room temperature
2. customthe reaction was quenched with aqueous saturated ammonium chloride (50 mL)
3. extractionextracted with EtOAc (1×100 mL)
4. dry with materialThe organic layer was dried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated
7. custompurified by column chromatography on silica gel
8. washeluting with an EtOAc/Hexanes gradient

ORD record

ord-0386dc7641e64e91bc8c6637af27ef3d

Source dataset

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08329722B2