Dichloromethane → (3S)-3-amino-1-hydroxy-5-methoxy-3,4-dihydroquinolin-2(1H)-one, hydrochloride salt

Temperature

-30 °C

tert-Butyl N-(diphenylmethylene)-2-methoxy-6-nitro-L-phenylalaninate (58) To a solution of tert-butyl N-(diphenylmethylene)glycinate (56) (1.2 g, 4.2 mmol), 2-(bromomethyl)-1-methoxy-3-nitrobenzene (57) (0.86 g, 3.3 mmol) and O-allyl-N-(9-anthracenylmethyl)cinchonidinium bromide (0.21 g, 0.33 mmol) in DCM (10 mL) cooled at −30° C., was added CsOH (0.84 g, 5.0 mmol). (See E. J. Corey et al., Journal of the American Chemical Society 1997, 119, 12414-12415.) The reaction was stirred at −30° C. overnight. The mixture was warmed to 0° C., quenched with saturated aqueous ammonium chloride solution (5 mL) and diluted with DCM (5 mL). The aqueous layer was extracted with DCM (3×5 mL), and the combined organic layers were washed with water, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (Gradient: 0% to 20% EtOAc in heptane) to give the title compound as a yellow solid (1.32 g, 87%). APCI m/z 461.2 (M+1). 1H NMR (400 MHz, CDCl3) δ 1.41 (s, 9H), 3.49 (dd, J=13.5, 4.3 Hz, 1H), 3.55 (s, 3H), 3.63 (dd, J=13.6, 9.6 Hz, 1H), 4.29 (dd, J=9.6, 4.3 Hz, 1H), 6.64 (br d, J=6.4 Hz, 2H), 6.88 (m, 1H), 7.20-7.34 (m, 8H), 7.51-7.54 (m, 2H).

1. temperatureThe mixture was warmed to 0° C.
2. customquenched with saturated aqueous ammonium chloride solution (5 mL)
3. additiondiluted with DCM (5 mL)
4. extractionThe aqueous layer was extracted with DCM (3×5 mL)
5. washthe combined organic layers were washed with water
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customThe residue was purified by chromatography on silica gel (Gradient: 0% to 20% EtOAc in heptane)

ORD record

ord-84f56615da614d8c8b2752c2b30affbb

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08183238B2