Chloroform → Ethyl (s)-10-fluoro-3-methyl-7-oxo-2,3-dihydro-7h-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylate

Ethyl 3-dimethylamino-2-(2,3,4-trifluorobenzoyl)acrylate (15.0 g, 49.8 mmol) was dissolved in ethanol (30 ml), and to this solution, an ethanol (10 ml) solution of (S)-2-amino-1-propanol (4.50 g, 59.8 mmol) was added dropwise while stirring and cooling with ice. After completion of dripping, the reaction solution was stirred for 1 hour at room temperature and then concentrated under a reduced pressure. The residue obtained was dissolved in dimethyl sulfoxide (50 ml), and after adding spray-dried calcium fluoride (16 g) thereto, it was stirred at 120° C. for 26 hours. After letting the reaction suspension cool, the reaction suspension was concentrated under a reduced pressure, chloroform (200 ml) and water (200 ml) were added to the residue, and after performing a separation operation, the water layer was extracted using chloroform (200 ml). The combined organic layers were then washed with saturated saline solution (100 ml) and then dried over anhydrous sodium sulfate. After filtering, the filtrate was concentrated under a reduced pressure, the residue obtained was applied to a silica gel chromatography, and 5.60 g (39%) of the title compound was obtained as a white powder from a chloroform:methanol=50:1 eluate.

1. temperaturecooling with ice
2. stirringthe reaction solution was stirred for 1 hour at room temperature
3. concentrationconcentrated under a reduced pressure
4. customThe residue obtained
5. stirringit was stirred at 120° C. for 26 hours
6. temperaturecool
7. concentrationthe reaction suspension was concentrated under a reduced pressure, chloroform (200 ml) and water (200 ml)
8. additionwere added to the residue
9. extractionthe water layer was extracted
10. washThe combined organic layers were then washed with saturated saline solution (100 ml)
11. dry with materialdried over anhydrous sodium sulfate
12. filtrationAfter filtering
13. concentrationthe filtrate was concentrated under a reduced pressure
14. customthe residue obtained

ORD-Eintrag

ord-adb9d71351d0499188e32e68ebded6b6

Quelldatensatz

uspto-grants-2011_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07902226B2