Réaction #2439925

Équation de réaction

p-fluorphenylboronic acid

3-bromo-5-hydroxymethyl-pyridine

Na2CO3

→

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

Rendement 84.4%

Solvants

toluene

Conditions de réaction

Traitement

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

Mode opératoire

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.

Source