Реакция #2439925

Уравнение реакции

p-fluorphenylboronic acid

3-bromo-5-hydroxymethyl-pyridine

Na2CO3

→

3-(p-fluorophenyl)-5-hydroxymethyl-pyridine

Выход 84.4%

Растворители

toluene

Условия реакции

Обработка

1. 1
   Другоеthe biphasic reaction mixture
2. 2
   Температураwas cooled
3. 3
   Другоеthe organic layer was collected
4. 4
   Промывкаwashed with saturated NaCl
5. 5
   ПромывкаThe aqueous layer was washed with EtOAc
6. 6
   Другоеthe combined organic layers were dried on Na2SO4
7. 7
   ДругоеThe drying agent was removed by filtration
8. 8
   Другоеthe solvent was evaporated in vacuo
9. 9
   Другоеto give a dark oil which
10. 10
    Другоеwas purified by flash chromatography on silica gel (eluent: CH2Cl2/MeOH/NH4OH, 95/4.5/0.5)

Методика

To a solution of 3-bromo-5-hydroxymethyl-pyridine (3.3 g, 17.5 mmol) in toluene (35 ml) was added Pd(PPh3)4 (0.6 g, 0.52 mmol), an aqueous solution of Na2CO3 (17.5 ml of a 2M solution) and p-fluorphenylboronic acid (2.65 g, 19 mmol, dissolved in 8.5 ml EtOH). The mixture was heated at 80-90° C. for 1 hr and vigorously stirred. After the reaction was completed, the biphasic reaction mixture was cooled, the organic layer was collected and washed with saturated NaCl. The aqueous layer was washed with EtOAc and the combined organic layers were dried on Na2SO4. The drying agent was removed by filtration and the solvent was evaporated in vacuo to give a dark oil which was purified by flash chromatography on silica gel (eluent: CH2Cl2/MeOH/NH4OH, 95/4.5/0.5) and yielded 3-(p-fluorophenyl)-5-hydroxymethyl-pyridine (3.0 g, 84%). The product was converted into its monohydrochloride salt; the residue was dissolved in Et2O and treated with 16.5 eq of ethanolic HCl. The product 3-(p-fluorophenyl)-5-hydroxymethyl-pyridinium hydrochloride Q4-OH.HCl precipitated as a white solid which was collected by filtration and subsequent drying.

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