Water → HCID 22100599, compound

HRID 1457741Notes

Reaction equation

HRID 1457741 reaction equation
Br[C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([F:9])[N:3]=1.[F:10][C:11]1[CH:16]=[CH:15][C:14](B(O)O)=[CH:13][CH:12]=1.C(=O)(O)[O-].[Na+].O>COCCOC.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:9][C:4]1[CH:5]=[C:6]([CH3:8])[CH:7]=[C:2]([C:14]2[CH:15]=[CH:16][C:11]([F:10])=[CH:12][CH:13]=2)[N:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 2856454-Fluorophenylboronic acidHCID 516892Sodium BicarbonateHCID 299193662-Bromo-6-fluoro-4-methylpyridine

Product 1

HCID 22100599HCID 22100599, compoundYield 36.1%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of 2-bromo-6-fluoro-4-methylpyridine (9.5 g, 50 mmol), 4-fluorobenzeneboronic acid (7.8 g, 56 mmol), sodium bicarbonate (12.6 g, 150 mmol), water (200 mL) and catalytic amounts of tetrakis(triphenylphosphine)palladium(0) in DME under nitrogen is heated to reflux overnight. After filtration of the reaction mixture the solvents are removed under reduced pressure. The residue is partitioned between water and ethyl acetate. The layers are separated and the aqueous layer is washed with ethyl acetate. After drying of the combined organic layers with anhydrous magnesium sulphate, the solvent is removed in vacuo. The crude product is purified by flash column chromatography (silica gel, pentane/ethyl acetate 9/1) yielding colorless crystals of 2-fluoro-6-(4'-fluorophenyl)-4-methylpyridine (3.7 g, 36.1% of th.) with mp 49° C.

Workup

  1. temperatureis heated
  2. temperatureto reflux overnight
  3. filtrationAfter filtration of the reaction mixture the solvents
  4. customare removed under reduced pressure
  5. customThe residue is partitioned between water and ethyl acetate
  6. customThe layers are separated
  7. washthe aqueous layer is washed with ethyl acetate
  8. dry with materialAfter drying of the combined organic layers with anhydrous magnesium sulphate
  9. customthe solvent is removed in vacuo
  10. customThe crude product is purified by flash column chromatography (silica gel, pentane/ethyl acetate 9/1)

Sources & evidence

ORD record
ord-689cead4b2504195a26e5c291f8efb1e
Source dataset
uspto-grants-1998_12
Patent number
US05849758

Reaction notes

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