Ethanol → 3-Acetyl-5-bromopyridine

HRID 1494306Notes

Reaction equation

HRID 1494306 reaction equation
[CH2:1](C(CC)(C([O-])=O)C([O-])=O)C.C(O)C.[Mg].[Br:16][C:17]1[CH:18]=[N:19][CH:20]=[C:21]([CH:25]=1)[C:22](Cl)=[O:23].S(=O)(=O)(O)O>CCOCC.C(Cl)(Cl)(Cl)Cl.O1CCCC1>[Br:16][C:17]1[CH:25]=[C:21]([C:22](=[O:23])[CH3:1])[CH:20]=[N:19][CH:18]=1

Participants

9

Reactant 5

HCID 702EthanolHCID 1118Sulfuric AcidHCID 27812235-Bromonicotinoyl chlorideHCID 5462224MagnesiumHCID 69515632,2-Diethylpropanedioate

Product 1

HCID 8204233-Acetyl-5-bromopyridine

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 5943Carbon TetrachlorideSolventHCID 8028TetrahydrofuranSolvent

Procedure

44.2 g (0.276 mol) of diethylmalonate, 19.9 g (0.432 mol) of absolute ethanol and 7 g (0.288 mol) of magnesium chips are refluxed for 18 hours with stirring in 254 ml of ether and 1.27 ml of carbon tetrachloride. To this solution, 55.3 g (0.25 mol) of 5-bromonicotinic acid chloride in 170 ml of absolute tetrahydrofuran are slowly added dropwise and refluxed for a further hour. The reaction mixture is cooled in an ice bath and carefully mixed with 508 ml of 2N sulphuric acid. The organic phase is separated off, dried over sodium sulphate and concentrated by evaporation. The residue is taken up in 83 ml of water, 127 ml of glacial acetic acid and 16.6 ml of concentrated sulphuric acid and refluxed for 18 hours. The reaction solution is evaporated down, the residue is diluted with 200 ml of water and adjusted to pH 8 with sodium hydroxide solution. It is then extracted with chloroform, dried over sodium sulphate and evaporated down.

Workup

  1. temperaturerefluxed for a further hour
  2. temperatureThe reaction mixture is cooled in an ice bath
  3. customThe organic phase is separated off
  4. dry with materialdried over sodium sulphate
  5. concentrationconcentrated by evaporation
  6. temperature127 ml of glacial acetic acid and 16.6 ml of concentrated sulphuric acid and refluxed for 18 hours
  7. customThe reaction solution is evaporated down
  8. additionthe residue is diluted with 200 ml of water
  9. extractionIt is then extracted with chloroform
  10. dry with materialdried over sodium sulphate
  11. customevaporated down

Sources & evidence

ORD record
ord-d57fe92b386748268d3a9e67e367d691
Source dataset
uspto-grants-1991_06
Patent number
US05026702

Reaction notes

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