4-Quinolinecarboxaldehyde → HCID 86716085, compound

Temperature

0 °C

Analogous to the general method described in J. Org. Chem. 2004, 69, 8115 and Chem. Pharm. Bull 1997, 1145. To a 2-necked flask containing 5-bromo-1-methyl-1H-imidazole (2.05 g, 12.7 mmol) was added THF (50 mL) and the solution was cooled to 0° C. To this clear homogeneous solution was added isopropyl magnesium chloride-LiCl complex (1.3 M, 10.5 mL, 13.6 mmol) which initially resulted in a white suspension, but became grayish once the addition of the Grignard reagent was complete. The reaction was stirred in an ice bath for 30 min, then a THF solution (20 mL) of quinoline-4-carbaldehyde (1.00 g, 6.36 mmol) was introduced and the reaction mixture became a greenish-grey color, and was subsequently allowed to warm to room temp. After 2 hours, the reaction mixture became brown in color and still remained heterogeneous. The reaction was quenched after 2 hours with saturated NH4Cl solution and the aqueous portion was extracted with EtOAc (4×75 mL). The combined organics were washed with brine, dried over MgSO4, filtered and concentrated to give an amber oil which solidified to a white solid upon standing. The crude material was triturated with DCM and then MeOH leaving behind the title compound as a white solid. The mother liquors were concentrated and chromatographed on silica gel (30% EtOAc-DCM increasing gradient to 10% MeOH-DCM) to provide more title compound as an off-white solid.

1. additionTo this clear homogeneous solution was added isopropyl magnesium chloride-LiCl complex (1.3 M, 10.5 mL, 13.6 mmol) which
2. custominitially resulted in a white suspension
3. temperatureto warm to room temp
4. waitAfter 2 hours
5. customThe reaction was quenched after 2 hours with saturated NH4Cl solution
6. extractionthe aqueous portion was extracted with EtOAc (4×75 mL)
7. washThe combined organics were washed with brine
8. dry with materialdried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated
11. customto give an amber oil which
12. customThe crude material was triturated with DCM
13. concentrationThe mother liquors were concentrated
14. customchromatographed on silica gel (30% EtOAc-DCM increasing gradient to 10% MeOH-DCM)

ORD record

ord-4b567ef8c8db49ab86219b89c95026cb

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09309222B2