Ethyl Bromide → 2-[2-(2,5-Dimethylphenoxymethyl)-alpha-hydroxybenzyl]pyridine

HRID 369117Notes

Reaction equation

HRID 369117 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][O:9][C:10]1[CH:15]=[C:14]([CH3:16])[CH:13]=[CH:12][C:11]=1[CH3:17].[Mg].Br[CH2:20][CH3:21].[Cl-].[NH4+:23].[CH2:24]1[CH2:28][O:27][CH2:26][CH2:25]1>>[CH3:17][C:11]1[CH:12]=[CH:13][C:14]([CH3:16])=[CH:15][C:10]=1[O:9][CH2:8][C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[CH:26]([C:25]1[CH:24]=[CH:28][CH:21]=[CH:20][N:23]=1)[OH:27]

Participants

6

Reactant 5

HCID 6332Ethyl BromideHCID 8028Tetrahydrofuran3×HCID 25517Ammonium ChlorideHCID 5462224MagnesiumHCID 109462162-Bromobenzyl-(2,5-dimethylphenyl)ether

Product 1

HCID 155451342-[2-(2,5-Dimethylphenoxymethyl)-alpha-hydroxybenzyl]pyridineYield 75.8%

Conditions

Temperature
52.5 °C

Procedure

A mixture of 2.91 g (0.01 mol) of 1-bromo-2-(2,5-dimethylphenoxymethyl) benzene and 8 ml of THF was added to a suspension of 0.36 g (0.015 mol) of magnesium, 0.1 ml of bromoethane, and 2 ml of tetrahydrofuran at 45 to 55° C. over 5 minutes under a nitrogen gas atmosphere and stirred at 50 to 55° C. for an hour to prepare a Grignard's reagent. The Grignard's reagent was added to a mixture of 1.18 g (0.011 mol) of 2-pyridinecarboxyaldehyde and 10 ml of THF below 5° C. over 15 minutes and stirred at room temperature for 2 hours. After completion of the reaction, 150 ml of an aqueous solution of ammonium chloride was added and extracted with 150 ml of ether. After the extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure, the residue thus obtained was purified by column chromatography on silica gel (ethyl acetate/n-hexane) to give 2.42 g of 2-[2-(2,5-dimethylphenoxymethyl)-α-hydroxybenzyl]pyridine (75.8% yield) as colorless oil.

Workup

  1. customto prepare a Grignard's reagent
  2. stirringstirred at room temperature for 2 hours
  3. additionwas added
  4. extractionextracted with 150 ml of ether
  5. dry with materialAfter the extract was dried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customthe residue thus obtained
  8. customwas purified by column chromatography on silica gel (ethyl acetate/n-hexane)

Sources & evidence

ORD record
ord-148acbfe0578434bbbea04fe0df4d251
Source dataset
uspto-grants-2000_10
Patent number
US06136837

Reaction notes

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