2-Bromo-4-methylpyridine → (2-Fluoro-4-methylphenyl)(4-methyl-pyridin-2-yl)methanol

HRID 593383Notes

Reaction equation

HRID 593383 reaction equation
Br[C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][N:3]=1.C([Li])CCC.[F:14][C:15]1[CH:22]=[C:21]([CH3:23])[CH:20]=[CH:19][C:16]=1[CH:17]=[O:18]>C(OCC)C>[F:14][C:15]1[CH:22]=[C:21]([CH3:23])[CH:20]=[CH:19][C:16]=1[CH:17]([C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][N:3]=1)[OH:18]

Participants

5

Reactant 3

HCID 27340872-Bromo-4-methylpyridineHCID 27784712-Fluoro-4-methylbenzaldehydeHCID 178418339Butyllithium

Product 1

HCID 86703873(2-Fluoro-4-methylphenyl)(4-methyl-pyridin-2-yl)methanol

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

To a solution of 2-bromo-4-methylpyridine (600 mg) in diethyl ether (20 mL) at −78° C. is added a 2.3M solution of butyllithium in hexanes (1.52 mL). After stirring at this temperature for 1 hour 2-fluoro-4-methylbenzaldehyde is added and the mixture allowed to warm at room temperature. The reaction mixture is then hydrolyzed with diluted aqueous hydrochloric acid, washed with diethyl ether, basified with concentrated sodium hydroxide and extracted with diethyl ether. The pooled organic extracts are dried over magnesium sulfate and concentrated under reduced pressure. The residue is purified by chromatography over silica gel (heptane/ethyl acetate 2/1) to afford (2-fluoro-4-methylphenyl)(4-methyl-pyridin-2-yl)methanol as a pale yellow oil which solidifies on standing.

Workup

  1. additionis added
  2. washhydrolyzed with diluted aqueous hydrochloric acid, washed with diethyl ether
  3. extractionextracted with diethyl ether
  4. dry with materialThe pooled organic extracts are dried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue is purified by chromatography over silica gel (heptane/ethyl acetate 2/1)

Sources & evidence

ORD record
ord-074df675293540b282da776a35ed39e4
Source dataset
uspto-grants-2016_01
Patent number
US09242959B2

Reaction notes

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