Nitric Acid → HCID 10631124, Verbindung

Temperatur

-10 °C

A 25-mL rb flask containing (R/S)-4-ethyl-1,2,3,4,-tetrahydroquinoline (340 mg, 2.1 mmol) was cooled to -10° C., and conc. H2SO4 (5 mL) was added slowly. The resulting solution was warmed to rt to effect complete dissolution of the quinoline, then cooled again to -10° C. and stirred vigorously. Fuming HNO3 (85 μL) was added dropwise, slowly, and the reaction mixture turned dark red. After 10 min, the reaction mixture was poured onto cracked ice and diluted with water (5 mL). Sat'd NaHCO3 (80 mL) was added, and the pH was adjusted to pH 9 with 3.0M NaOH. This aqueous phase was extracted with EtOAc (3×75 mL), and the combined extracts were dried (Na2SO4),and concentrated under reduced pressure to yield a dark red oil. This crude material was placed into a 250-mL rb flask with 1:1 EtOAc/EtOH (40 mL) and 10% Pd on C (approx. 1 mol %). The vessel was evacuated and flushed with nitrogen three times, then stirred under an atmosphere of hydrogen for 16 h, filtered, and concentrated under reduced pressure to yield a yellow oil, which was purified by flash chromatography (silica gel, CH2 Cl2 /methanol, 9:1), affording 210 mg (57%) of the desired product as a dark yellow oil (Rf 0.50, CH2Cl2 /MeOH, 9:1). Data for (R/S)-7-amino-4-ethyl-1,2,3,4,-tetrahydroquinoline: 1H NMR (400 MHz, CDCl3) 6.81 (d, 1H, J=8.1, 5-H), 6.02 (dd, 1H, J=8.0, 2.2, 6-H), 5.84 (d, 1H, J=2.3, 8-H), 3.48 (s, 2H, NH2), 3.27 (ddd, 1H, J=11.1, 11.1, 3.5, 2-H), 3.20 (ddd, 1H, J=9.8, 5.3, 4.5, 2-H), 2.55 (dddd, 1H, J=10.2, 5.2, 5.2, 5.2, 4H), 1.90 (dddd, 1H, J=9.6, 9.6, 9.6, 4.7, 3-H), 1.72 (m, 2H, 3-H, CH2CH3), 1.48 (m, 1H, CH2CH3), 0.96 (t, 3H, J=7.4, CH3).

1. temperatureThe resulting solution was warmed to rt
2. temperaturecooled again to -10° C.
3. additionthe reaction mixture was poured
4. extractionThis aqueous phase was extracted with EtOAc (3×75 mL)
5. concentrationconcentrated under reduced pressure
6. customto yield a dark red oil
7. customThe vessel was evacuated
8. customflushed with nitrogen three times
9. stirringstirred under an atmosphere of hydrogen for 16 h
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure
12. customto yield a yellow oil, which
13. customwas purified by flash chromatography (silica gel, CH2 Cl2 /methanol, 9:1)

ORD-Eintrag

ord-1b5ea510e169490986bf3df4af2f3f6e

Quelldatensatz

uspto-grants-1997_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US05696127