Реакция #162568

Уравнение реакции

potassium phthalimide

2-(1-bromoethyl)-3-chloro-6-fluoroquinoxaline

3-chloro-2-(1-chloroethyl)-6-fluoroquinoxaline

N,N-dimethylformamide

→

2-(1-(3-chloro-6-fluoroquinoxalin-2-yl)ethyl)isoindoline-1,3-dione

Выход 76.0%

Растворители

water

Условия реакции

Обработка

1. 1
   workup.WAITAfter 1 h
2. 2
   ЭкстракцияThe mixture was extracted with DCM (500 mL×3)
3. 3
   ПромывкаThe combined organic layers were washed with brine (1 L×1)
4. 4
   Сушкаdried over MgSO4
5. 5
   Фильтрацияfiltered
6. 6
   Концентрированиеconcentrated under reduced pressure
7. 7
   Другоеto give a red liquid
8. 8
   ФильтрацияThe red liquid was filtered though a plug of silica (5.5 inch diameter×5 inch height)
9. 9
   Другое30% of EtOAc in hexane, and then 100% of EtOAc as eluent to give two fractions

Методика

To a mixture of 2-(1-bromoethyl)-3-chloro-6-fluoroquinoxaline (57.17 g, 197.5 mmol) containing 3-chloro-2-(1-chloroethyl)-6-fluoroquinoxaline (48.39 g, 197.5 mmol) in N,N-dimethylformamide (700.0 ml, 197.5 mmol) was added potassium phthalimide (91.43 g, 493.6 mmol) at rt and the mixture was stirred at rt for 1 h. After 1 h, to the mixture was added water (2 L). The mixture was extracted with DCM (500 mL×3). The combined organic layers were washed with brine (1 L×1), dried over MgSO4, filtered, and concentrated under reduced pressure to give a red liquid. The red liquid was filtered though a plug of silica (5.5 inch diameter×5 inch height), and eluented with 20% of EtOAc in hexane, then 30% of EtOAc in hexane, and then 100% of EtOAc as eluent to give two fractions. Second fraction, desired product 2-(1-(3-chloro-6-fluoroquinoxalin-2-yl)ethyl)isoindoline-1,3-dione (53.367 g, 75.97% yield) as a pink solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.25 (dd, J=9.4, 5.9 Hz, 1H), 7.81-7.95 (m, 6H), 5.86 (q, J=6.8 Hz, 1H), 1.86 (d, J=7.0 Hz, 3H). Mass Spectrum (ESI) m/e=356.0 (M+1).

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