Реакция #683135

Уравнение реакции

tert-butyl 2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate

2-amino-3-chloropyrazine

sodium carbonate

DME

→

tert-butyl 4-(3-aminopyrazin-2-yl)-2-fluorobenzoate

Выход 86.3%

Растворители

water

Условия реакции

Обработка

1. 1
   ДругоеThe reaction mixture was degassed for 10 min
2. 2
   Температураmaintained at this temperature for 4 h
3. 3
   ТемператураAfter cooling down
4. 4
   Экстракцияextracted with EtOAc (3×200 mL)
5. 5
   ПромывкаThe combined organics were washed with brine (3×200 mL)
6. 6
   Сушкаdried over magnesium sulfate
7. 7
   Фильтрацияfiltered
8. 8
   Концентрированиеconcentrated
9. 9
   ДругоеThe crude material was purified
10. 10
    Другоеon silica gel (0 to 70% EtOAc in heptane over 50 min)

Методика

A 2 L round-bottomed flask was charged with tert-butyl 2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (54 g, 151 mmol), 2-amino-3-chloropyrazine (19.54 g, 151 mmol), 2 N sodium carbonate (158 mL, 317 mmol) and DME (600 mL). The reaction mixture was degassed for 10 min using argon, and then PdCl2(dppf)-CH2Cl2 (6.16 g, 7.54 mmol) was added. The reaction mixture was heated to 100° C. and maintained at this temperature for 4 h. After cooling down, the reaction mixture was poured into water (400 mL) and extracted with EtOAc (3×200 mL). The combined organics were washed with brine (3×200 mL), dried over magnesium sulfate, filtered and concentrated. The crude material was purified using flash chromatography on silica gel (0 to 70% EtOAc in heptane over 50 min), giving tert-butyl 4-(3-aminopyrazin-2-yl)-2-fluorobenzoate (37.7 g, 86%) as a solid. LCMS (m/z): 290 (MH+), 0.80 min; 1H NMR (400 MHz, DMSO-d6) δ ppm 7.98 (d, 1H) 7.91-7.81 (m, 2H) 7.65-7.46 (m, 2H) 6.35 (br. s., 2H) 1.54 (s, 9H).

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