Ethyl chloroformate → HCID 57043689, compound

8-Chloro-4-methoxyquinoline (1.0 g, 5.2 mmol, dissolved in 6 mL of anhydrous tetrahydrofuran) was added dropwise via cannula to a solution of methyllithium (18.4 mL of a 1.4 M solution in diethyl ether) cooled with an ice/water bath. After 45 min, ethyl chloroformate (4.9 mL, 51.7 mmol) was added to the reaction mixture via syringe. After 1.5 hours, the reaction mixture was quenched with 60 mL of a 1N aqueous HCl solution, 100 mL of THF and 20 mL of methanol. After 3 days, the tetrahydrofuran was removed in vacuo, and the remaining aqueous phase was extracted with ethyl acetate (3×100 mL). The organic phases were combined and washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo to give 1.5 g of crude product. Purification by silica gel chromatography using 0-20% ethyl acetate/hexanes as eluent afforded 0.79 g of the title product (57%). 1H NMR (CDCl3) δ 1.2 (d, 3H), 1.3 (t, 3H), 2.6 (d, 1H), 3.1 (dd, 1H), 4.2-4.4 (m, 2H), 5.1-5.2 (m, 1H), 7.2 (d, 1H), 7.6 (d, 1H), 7.9 (d, 1H).

1. temperaturecooled with an ice/water bath
2. waitAfter 1.5 hours
3. customthe reaction mixture was quenched with 60 mL of a 1N aqueous HCl solution, 100 mL of THF and 20 mL of methanol
4. waitAfter 3 days
5. customthe tetrahydrofuran was removed in vacuo
6. extractionthe remaining aqueous phase was extracted with ethyl acetate (3×100 mL)
7. washwashed with brine
8. dry with materialdried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customto give 1.5 g of crude product
12. customPurification by silica gel chromatography

ORD record

ord-7ee593552e75426199cd913d078c4fde

Source dataset

uspto-grants-2002_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06395751B1