Acetaldehyde → 1-(2,8-Dichloroquinolin-3-yl)ethanol

To a cold solution of diisopropylamine (6.6 mL, 1.1 eq) in THF (100 mL) was added dropwise a solution of BunLi (1.1 eq, 2.5 M, 18.7 mL) in hexane at −20° C. The resulted LDA solution was kept in 0° C. for 30 min and cooled to −78° C. before addition of a solution of 2,8-dichloroquinoline (8.4 g, 42.4 mmol) in THF (44 mL) dropwise. The temperature was controlled below −72° C. by adjusting of adding rate (15 min). After 45 min, MeCHO (3.6 mL, 1.5 eq) was added dropwise. After 30 min, the reaction was quenched with NH4Cl and partitioned between EtOAc (150 mL) and water (100 mL). The combined organics were washed with water, brine, dried over Na2SO4. Removal of solvent gave colorless oil which was purified by column chromatography on silica gel (DCM/Hexane, 3/2) to give an oil. Hexane was added (80 mL) and the mixture was left over night. Filtration gave a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 8.43 (s, 1H), 7.84 (d, J=8.0 Hz, 1H), 7.79 (d, J=8.0 Hz, 1H), 7.50 (t, J=8.0 Hz, 1H), 5.40 (q, J=8.0 Hz, 1H), 1.63 (d, J=8.0 Hz, 3H). Mass Spectrum (ESI) m/e=242 (M+1).

1. customwas controlled below −72° C.
2. additionof adding rate (15 min)
3. waitAfter 30 min
4. customthe reaction was quenched with NH4Cl
5. custompartitioned between EtOAc (150 mL) and water (100 mL)
6. washThe combined organics were washed with water, brine
7. dry with materialdried over Na2SO4
8. customRemoval of solvent
9. customgave colorless oil which
10. customwas purified by column chromatography on silica gel (DCM/Hexane, 3/2)
11. customto give an oil
12. waitthe mixture was left over night
13. filtrationFiltration
14. customgave a white solid

ORD record

ord-b20bb530ffd845d8bbda4c3739841b71

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08586739B2