Diisopropylamine → Ethyl (6-bromo-2-quinolinyl)acetate

To a solution of diisopropylamine (19.2 g, 0.19 mole) in diethyl ether (200 mL) was added 2.5 M n-butyllithium in hexane (74 mL, 0.185 mole) at −78° C. The clear solution was mixed for 30 min, and followed by addition of 6-bromo-2-methyl-quinoline (13.32 g, 0.060 mole) in ether (200 mL) slowly at −78° C. The brown solution was stirred for 0.5 hour, and ethyl chloroformate (7.45 g, 0.069 mole) in ether (50 mL) was syringed into the mixture slowly so that the internal temperature did not exceed −70° C. The yellow reaction mixture was quenched by addition of 50 mL water, allowed to warm up to rt, and diluted with ethyl acetate (300 mL). The solution was washed with 5% sodium bicarbonate aq. solution (700 mL×3), 25% brine (700 mL), dried over MgSO4, and filtered. The organic was concentrated to ˜50 mL volume, and the slurry diluted with heptane (50 mL). The slurry was stirred at 0° C. for 2 h, and the solid was collected by filtration, rinsed with a ice-cold heptane: ethyl acetate (10 mL, 2:1), dried at 50° C. under vacuum to give a yellow solid (12.0 g). Concentration of the mother liquid afforded a 2nd crop of the product (3.6 g). Total yield: 88%; mp: 100-101° C. (uncorrected); MS (ESI): 294, 296 (M+H)+; 1H-NMR (CDCl3) δ 8.02 (1H, d, J=8.5 Hz), 7.94 (1H, d, J=2.2 Hz), 7.91 (1H, d, J=8.9 Hz), 7.74 (1H, dd, J=8.9, 2.2 Hz), 7.44 (1H, d, J=8.5 Hz), 4.20 (2H, q, J=7.1 Hz), 4.01 (2H, s), 1.27 (3H, t, J=7.1 Hz); 13C-NMR (CDCl3) δ169.7, 154.9, 146.0, 135.1, 132.6, 130.5, 128.9, 127.8, 122.3, 119.9, 61.2, 44.9, 14.5.

1. additionThe clear solution was mixed for 30 min
2. customdid not exceed −70° C
3. customThe yellow reaction mixture was quenched by addition of 50 mL water
4. additiondiluted with ethyl acetate (300 mL)
5. washThe solution was washed with 5% sodium bicarbonate aq. solution (700 mL×3), 25% brine (700 mL)
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationThe organic was concentrated to ˜50 mL volume
9. additionthe slurry diluted with heptane (50 mL)
10. stirringThe slurry was stirred at 0° C. for 2 h
11. filtrationthe solid was collected by filtration
12. washrinsed with a ice-cold heptane
13. dry with materialethyl acetate (10 mL, 2:1), dried at 50° C. under vacuum

ORD-Eintrag

ord-6a6e29ff88604800a23de2fd3d4e82ae

Quelldatensatz

uspto-grants-2011_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07947711B2