Реакция #73023

Уравнение реакции

dibenzylamine

HCl

1-{[(2-chloro-5,6-dimethyl-3-nitropyridin-4-yl)amino]methyl}cyclohexanol

dibenzylamine

triethylamine

→

1-({[2-(dibenzylamino)-5,6-dimethyl-3-nitropyridin-4-yl]amino}methyl)cyclohexanol

Выход 79.0%

Растворители

diethyl ether

methanol

ethyl acetate

toluene

Условия реакции

Обработка

1. 1
   Температураat reflux for 7 d
2. 2
   ДругоеThe volatiles were removed under reduced pressure
3. 3
   Другоеthe residue was partitioned between chloroform (300 mL) and water (100 mL)
4. 4
   ЭкстракцияThe aqueous layer was extracted with chloroform (2×75 mL)
5. 5
   ПромывкаThe combined organic layers were washed with brine (50 mL)
6. 6
   Сушкаdried over MgSO4
7. 7
   Фильтрацияfiltered
8. 8
   Концентрированиеconcentrated
9. 9
   Другоеto give a semi-solid
10. 10
    ДругоеThe semi-solid was triturated with 1:2 ethyl acetate/hexanes
11. 11
    Фильтрацияfiltered
12. 12
    КонцентрированиеThe filtrate was concentrated to an orange oil that
13. 13
    Другоеwas purified on a Biotage (gradient elution, 0-30% ethyl acetate/hexanes)
14. 14
    Другоеto yield an oil
15. 15
    Другоеthe solvent was removed in vacuo
16. 16
    ДругоеThe residue was triturated with 1:2 ethyl acetate/hexanes
17. 17
    Фильтрацияfiltered
18. 18
    КонцентрированиеThe filtrate was concentrated
19. 19
    workup.DISSOLUTIONthe resulting oil was dissolved in chloroform (300 mL)
20. 20
    Промывкаwashed with saturated aqueous sodium bicarbonate (50 mL)
21. 21
    Сушкаdried over MgSO4
22. 22
    Фильтрацияfiltered
23. 23
    Концентрированиеconcentrated
24. 24
    workup.DISSOLUTIONThe material was dissolved in ethyl acetate (400 mL)
25. 25
    Промывкаwashed with 10% aqueous citric acid (2×100 mL), saturated aqueous sodium bicarbonate (50 mL) and brine (50 mL)
26. 26
    Сушкаdried over MgSO4
27. 27
    Фильтрацияfiltered
28. 28
    Концентрированиеconcentrated in vacuo

Методика

A solution of 1-{[(2-chloro-5,6-dimethyl-3-nitropyridin-4-yl)amino]methyl}cyclohexanol (prepared as described in Part A, 27.1 mmol), dibenzylamine (15.6 mL, 81.3 mmol), and triethylamine (5.67 mL, 40.7 mmol) in toluene (100 mL) was heated at reflux for 7 d. The volatiles were removed under reduced pressure and the residue was partitioned between chloroform (300 mL) and water (100 mL). The aqueous layer was extracted with chloroform (2×75 mL). The combined organic layers were washed with brine (50 mL), dried over MgSO4, filtered, and concentrated to give a semi-solid. The semi-solid was triturated with 1:2 ethyl acetate/hexanes and filtered. The filtrate was concentrated to an orange oil that was purified on a Biotage (gradient elution, 0-30% ethyl acetate/hexanes) to yield an oil contained both product and dibenzylamine. The oil was dissolved in ethyl acetate (100 mL) and 1 M HCl in diethyl ether (50 mL) and methanol (100 mL) were added. The solution was stirred for 10 minutes and the solvent was removed in vacuo. The residue was triturated with 1:2 ethyl acetate/hexanes and filtered. The filtrate was concentrated, and the resulting oil was dissolved in chloroform (300 mL), washed with saturated aqueous sodium bicarbonate (50 mL), dried over MgSO4, filtered, and concentrated. The material was dissolved in ethyl acetate (400 mL) and washed with 10% aqueous citric acid (2×100 mL), saturated aqueous sodium bicarbonate (50 mL) and brine (50 mL), dried over MgSO4, filtered, and concentrated in vacuo to yield 1-({[2-(dibenzylamino)-5,6-dimethyl-3-nitropyridin-4-yl]amino}methyl)cyclohexanol (10.14 g, 79% yield over two steps).

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