Sodium Carbonate → [5-(4-Fluorophenyl)pyridin-3-yl]methanol

HRID 2288627Notes

Reaction equation

HRID 2288627 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH2:8][OH:9])[CH:7]=1.C([O-])([O-])=O.[Na+].[Na+].[F:16][C:17]1[CH:22]=[CH:21][C:20](B(O)O)=[CH:19][CH:18]=1>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:16][C:17]1[CH:22]=[CH:21][C:20]([C:2]2[CH:3]=[N:4][CH:5]=[C:6]([CH2:8][OH:9])[CH:7]=2)=[CH:19][CH:18]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 2784733(5-Bromo-3-pyridinyl)methanol

Product 1

HCID 15541798[5-(4-Fluorophenyl)pyridin-3-yl]methanolYield 84.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
85 °C

Procedure

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.

Workup

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

Sources & evidence

ORD record
ord-a0bf446ba7ac4dd3a83a08d97363ba1d
Source dataset
uspto-grants-2000_07
Patent number
US06090812

Reaction notes

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