Dimethylformamide → HCID 17974702, Verbindung

Temperatur

-78 °C

A flask was charged with 4-bromo-3-chloroquinoline (A275-2) (1.00 g, 4.12 mmol) and THF (16.5 mL) under nitrogen, and the solution was cooled to −78° C. To the cooled mixture was added n-butyllithium (2.5 M solution in hexane, 1.65 mL, 4.12 mmol) and the mixture was stirred at −78° C. for 1 hour. To the mixture was added DMF (1.60 mL, 20.6 mmol) dropwise, and the mixture was allowed to warm to room temperature. After 4 h, the mixture was quenched with saturated aqueous NH4Cl (20 mL). The mixture was partitioned between water (50 mL) and EtOAc (50 mL). The aqueous layer was extracted with EtOAc (1×50 mL). The organic extract was dried over MgSO4. The solution was filtered and concentrated in vacuo to give the crude material as a brown syrup. The crude material was absorbed onto a plug of silica gel and purified by chromatography through a REDISEP™ pre-packed silica gel column (80 g), eluting with a gradient of 0% to 20% EtOAc in hexane, and dried under high vacuum to give 3-chloroquinoline-4-carbaldehyde (A275-3) as brown solid. 1H NMR (400 MHz, DMSO-d6) δ 10.74 (1H, s), 9.10 (1H, s), 8.68-8.73 (1H, m), 8.15 (1H, dd, J=8.5, 0.9 Hz), 7.79-7.92 (2H, m); LCMS (ESI) m/z 192.1 (M+H)+.

1. temperatureto warm to room temperature
2. waitAfter 4 h
3. customthe mixture was quenched with saturated aqueous NH4Cl (20 mL)
4. customThe mixture was partitioned between water (50 mL) and EtOAc (50 mL)
5. extractionThe aqueous layer was extracted with EtOAc (1×50 mL)
6. extractionThe organic extract
7. dry with materialwas dried over MgSO4
8. filtrationThe solution was filtered
9. concentrationconcentrated in vacuo
10. customto give the crude material as a brown syrup
11. customThe crude material was absorbed onto a plug of silica gel
12. custompurified by chromatography through a REDISEP™ pre-packed silica gel column (80 g)
13. washeluting with a gradient of 0% to 20% EtOAc in hexane
14. customdried under high vacuum

ORD-Eintrag

ord-68f7578b0b6b41ff9eb8fa46bdee3f8a

Quelldatensatz

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09365522B2