Ethyl Acetate → Ethyl 6-trifluoromethyl-1,2-dihydro-2-(trifluoromethyl)-3-quinolinecarboxylate

Temperatur

30 °C

To a suspension of N-(2-formyl-4-(trifluoro-methylphenyl)-2,2-dimethyl propanamide (Step 2) (921 mg, 3.7 mol) and lithium hydride (115 mg, 14.5 mmol) in dimethyl sulfoxide (10 mL) was added ethyl 4,4,4-trifluorocrotonate (2.83 g, 16.8 mmol) and the contents warmed to 30° C. for 4 hours. After the addition of ethyl acetate (50 mL), the reaction was washed with water (2×30 mL), saturated ammonium chloride solution (2×30 mL), dried over sodium sulfate and filtered. The filtrate was concentrated in vacuo to afford a yellow solid. The product was purified by flash chromatography (silica gel, eluant: ethyl acetate-hexanes, 1:9) to yield, upon concentration of the appropriate fractions, ethyl 6-trifluoromethyl-1,2-dihydro-2-(trifluoromethyl)-3-quinolinecarboxylate as a yellow solid (65 mg, 5%): mp 138-139° C. 1H NMR (CDCl3/300 MHz) 7.67 (s, 1H), 7.26 (s, 1H), 7.04 (d, 1H, J=6.6 Hz), 6.62 (m, 1H,), 5.14 (m, 1H), 4.60 (brs, 1H), 4.32 (m, 2H), 1.35 (t, 3H, J=7.0 Hz). ESHRMS m/z 338.0592 (M−H, Calc'd 338.0616). Anal. Calc'd for C13H11F3NO2: C, 49.57; H, 3.27; N, 4.13; Found: C, 49.23; H, 2.81; N, 3.93.

1. washthe reaction was washed with water (2×30 mL), saturated ammonium chloride solution (2×30 mL)
2. dry with materialdried over sodium sulfate
3. filtrationfiltered
4. concentrationThe filtrate was concentrated in vacuo
5. customto afford a yellow solid
6. customThe product was purified by flash chromatography (silica gel, eluant: ethyl acetate-hexanes, 1:9)

ORD-Eintrag

ord-407e8853235c441f901578b9746d1b3d

Quelldatensatz

uspto-grants-2001_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06271253B1