Methanol → 2-Methyl-4-oxo-3,4-dihydro-2H-quinoline-1-carboxylic Acid Benzyl Ester

To a solution of 4-methoxy quinoline (3g) in tetrahydrofuran (80 ml), under nitrogen, and under cooling at −78° C. in an acetone-dry ice bath and under stirring, a solution of methyl magnesium chloride at 3 M/l in tetrahydrofuran was added dropwise (77 ml) for 30 minutes. The mixture was stirred for 30 minutes and then benzyl chloroformate (32.15 g) was added dropwise for 45 minutes at −78° C. The mixture was stirred at room temperature over night. The reaction mixture was hydrolyzed with methanol (200 ml) and then with HCl 1 mol/l (200 ml) and finally concentrated. Dichloromethane (200 ml) and aqueous solution of sodium bicarbonate were added to the mixture under stirring. The separate organic layer was washed with an aqueous solution of sodium chloride (200 ml). The solvent was removed under reduce pressure to give an oil, which was chromatographed in silica gel with an eluent of cyclohexane/ethyl acetate (95/5). The fractions containing the desired compound were combined and evaporated to give an oil (5.44 g, 98% yield).

1. stirringThe mixture was stirred for 30 minutes
2. stirringThe mixture was stirred at room temperature over night
3. concentrationwith HCl 1 mol/l (200 ml) and finally concentrated
4. additionDichloromethane (200 ml) and aqueous solution of sodium bicarbonate were added to the mixture
5. stirringunder stirring
6. washThe separate organic layer was washed with an aqueous solution of sodium chloride (200 ml)
7. customThe solvent was removed
8. customto give an oil, which
9. customwas chromatographed in silica gel with an eluent of cyclohexane/ethyl acetate (95/5)
10. additionThe fractions containing the desired compound
11. customevaporated

ORD record

ord-b8a04dcb7a154de6b0aebf01aa3c0a2c

Source dataset

uspto-grants-2007_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07220760B2