Reaktion #160795

Reaktionsgleichung

NaBH4

(4aR,8aR)-1-benzyl-4,4-diethoxyoctahydroquinolin-4a(2H)-ol

water

(4aR,8aS)-1-benzyl-4a-hydroxyoctahydroquinolin-4(1H)-one

aniline

camphorsulfonic acid

→

title compound

(4R,4aS,8aR)-1-benzyl-4-(phenylamino)octahydroquinolin-4a(2H)-ol

Lösungsmittel

EtOH

potassium carbonate

toluene

CH3COOH

DCE

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe reaction mixture was heated
2. 2
   Temperaturto reflux for 3 hrs
3. 3
   ExtraktionThe aqueous layer was extracted with ethyl acetate (3×20 mL)
4. 4
   WaschenThe combined organic fractions were washed with brine (saturated, 30 mL)
5. 5
   Sonstigedried
6. 6
   Filtrationfiltered
7. 7
   Sonstigethe solvent was evaporated under reduced pressure
8. 8
   TemperaturThe reaction was then cooled to rt
9. 9
   workup.STIRRINGThe mixture was then stirred overnight at rt
10. 10
    SonstigeThe mixture was then quenched with sat'd
11. 11
    Extraktionextracted 3× with EtOAc
12. 12
    SonstigeThe combined organics were dried
13. 13
    Filtrationfiltered
14. 14
    Einengenconcentrated
15. 15
    SonstigeThe residue was purified by column chromatography

Vorschrift

To (4aR,8aR)-1-benzyl-4,4-diethoxyoctahydroquinolin-4a(2H)-ol (200 mg, 0.600 mmol) in toluene (12.000 ml) at room temperature was added water (0.162 ml, 9.00 mmol) followed by camphorsulfonic acid (153 mg, 0.660 mmol). The reaction mixture was heated to reflux for 3 hrs. The reaction mixture was diluted with aqueous potassium carbonate (saturated, 30 mL). The aqueous layer was extracted with ethyl acetate (3×20 mL). The combined organic fractions were washed with brine (saturated, 30 mL), dried, filtered and the solvent was evaporated under reduced pressure. A mixture of (4aR,8aS)-1-benzyl-4a-hydroxyoctahydroquinolin-4(1H)-one (0.500 g, 1.93 mmol) and aniline (0.528 mL, 5.78 mmol) in 4% CH3COOH in DCE (10 mL) was stirred for 4 hr at 80° C. The reaction was then cooled to rt and NaBH4 (0.438 g, 11.6 mmol) was then added followed by the addition of EtOH (10 mL). The mixture was then stirred overnight at rt. The mixture was then quenched with sat'd. aq. NH4Cl. It was then basified with 2M Na2CO3 and extracted 3× with EtOAc. The combined organics were dried, filtered and concentrated. The residue was purified by column chromatography to give the title compound. 1H-NMR (500 MHz, CDCl3) δ 7.29-7.35 (m, 4H), 7.23-7.30 (m, 1H), 7.17 (t, 2H, J=8.3 Hz), 6.76-6.84 (m, 3H), 4.10 (d, 1H, J=8.0 Hz), 3.96 (d, 1H, J=13.2 Hz), 3.03 (d, 1H, J=13.2 Hz), 2.97 (s, 1H), 2.86 (t, 1H, J=7.8 Hz), 2.37 (d, 1H, J=6.8 Hz), 1.41-2.24 (m, 10H). HRMS (ES) m/z M±H calc'd: 337.2274. found: 337.2275.

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