Реакция #160795

Уравнение реакции

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

Растворители

EtOH

potassium carbonate

toluene

CH3COOH

DCE

Условия реакции

Обработка

1. 1
   ТемператураThe reaction mixture was heated
2. 2
   Температураto reflux for 3 hrs
3. 3
   ЭкстракцияThe aqueous layer was extracted with ethyl acetate (3×20 mL)
4. 4
   ПромывкаThe combined organic fractions were washed with brine (saturated, 30 mL)
5. 5
   Другоеdried
6. 6
   Фильтрацияfiltered
7. 7
   Другоеthe solvent was evaporated under reduced pressure
8. 8
   ТемператураThe reaction was then cooled to rt
9. 9
   workup.STIRRINGThe mixture was then stirred overnight at rt
10. 10
    ДругоеThe mixture was then quenched with sat'd
11. 11
    Экстракцияextracted 3× with EtOAc
12. 12
    ДругоеThe combined organics were dried
13. 13
    Фильтрацияfiltered
14. 14
    Концентрированиеconcentrated
15. 15
    ДругоеThe residue was purified by column chromatography

Методика

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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