Sodium Cyanide → 2-(2-Bromo-5-methoxyphenyl)acetonitrile

HRID 2275301Notes

Reaction equation

HRID 2275301 reaction equation
CO[C:3](=O)[C:4]1[CH:9]=[C:8]([O:10][CH3:11])[CH:7]=[CH:6][C:5]=1[Br:12].[H-].[H-].[H-].[H-].[Li+].[Al+3].CS(Cl)(=O)=O.[C-:25]#[N:26].[Na+]>C(Cl)Cl.CN(C=O)C.C1COCC1>[Br:12][C:5]1[CH:6]=[CH:7][C:8]([O:10][CH3:11])=[CH:9][C:4]=1[CH2:3][C:25]#[N:26]

Participants

8

Reactant 4

HCID 8929Sodium CyanideHCID 31297Methanesulfonyl chlorideHCID 2776849Methyl 2-bromo-5-methoxybenzoateHCID 21226445Aluminium lithium hydride

Product 1

HCID 6396662-(2-Bromo-5-methoxyphenyl)acetonitrileYield 67%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To the THF solution (1000 ml) of 2-bromo-5-methoxy-benzoic acid methyl ester (20 g, 81.6 mmol), the THF suspension (50 ml) of LAH (4.07 g, 102 mmol) was added under ice cooling. The mixture was stirred for 30 min under ice cooling. The reaction solution was partitioned between saturated aqueous solution of Na2SO4 and ethyl acetate. The organic layer was washed with saturated brine and concentrated under reduced pressure. The resulting residues were dissolved in DCM (200 ml), and added with TEA (12.51 ml, 89.76 mmol) and MsCl (6.63 ml, 85.68 mmol) under ice cooling, followed by stirring overnight at room temperature. The reaction mixture was diluted with DCM, and washed in order with 10% aqueous solution of citric acid, saturated aqueous solution of NaHCO3 and saturated brine. The residues obtained after concentration under reduced pressure were dissolved in DMF (100 ml), and added with the DMF (500 ml) solution of NaCN (40 g, 81.6 mmol) under ice cooling. After stirring for 2 hrs under ice cooling, the reaction mixture was extracted with ether, washed with saturated brine and dried over magnesium sulfate. The residues obtained after concentration under reduced pressure were purified by silica gel column (hexane:ethyl acetate=10:1) to obtain the title compound (12.1 g, 67%).

Workup

  1. customThe reaction solution was partitioned between saturated aqueous solution of Na2SO4 and ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe resulting residues were dissolved in DCM (200 ml)
  5. stirringby stirring overnight at room temperature
  6. washwashed in order with 10% aqueous solution of citric acid, saturated aqueous solution of NaHCO3 and saturated brine
  7. customThe residues obtained
  8. concentrationafter concentration under reduced pressure
  9. dissolutionwere dissolved in DMF (100 ml)
  10. stirringAfter stirring for 2 hrs under ice cooling
  11. extractionthe reaction mixture was extracted with ether
  12. washwashed with saturated brine
  13. dry with materialdried over magnesium sulfate
  14. customThe residues obtained
  15. concentrationafter concentration under reduced pressure
  16. customwere purified by silica gel column (hexane:ethyl acetate=10:1)

Sources & evidence

ORD record
ord-b0b491d525c949e5a10245cc9498437e
Source dataset
uspto-grants-2015_09
Patent number
US09126931B2

Reaction notes

Loading…