Hydrochloric Acid → 612070-27-6

HRID 1618876Notes

Reaction equation

HRID 1618876 reaction equation
[Mg].Br[C:3]1[CH:8]=[CH:7][C:6]([Br:9])=[CH:5][CH:4]=1.Br[C:11]1[CH:16]=[CH:15]C=CC=1.Cl.[C:18](=O)(O)[O-:19].[Na+].C1C[O:26]CC1>BrCCBr>[Br:9][C:6]1[CH:7]=[CH:8][C:3]([C:18](=[O:19])[C:16]([OH:26])([CH3:15])[CH3:11])=[CH:4][CH:5]=1

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 78041,4-DibromobenzeneHCID 7961BromobenzeneHCID 8028Tetrahydrofuran3×HCID 516892Sodium BicarbonateHCID 5462224Magnesium

Product 1

HCID 54135387612070-27-6

Reagents, catalysts & solvents 1

HCID 78391,2-DibromoethaneCatalyst

Procedure

In a dry 250 ml three necked flask was placed magnesium turnings (2.46 g, 101.2 mmol), 5 ml dry THF and two drops of 1,2-dibromoethane, stirred under N2 at room temperature. Subsequently 1,4-dibromobenzene (19.8 g, 84 mmol) in 15 ml dry THF was added dropwise over 30 min. An ice water bath was occasionally used to moderate the reaction. After addition was complete the reaction was stirred for 2 hrs to complete conversion of bromobenzene. A solution of 2-methyl-2-trimethylsilanyloxy-1-propionitrile (13.25 g, 85 mmol) in 15 ml dry THF was added dropwise to the Grignard reagent and the mixture was stirred for 20 hrs. By this time a large quantity of white precipitate was formed. The intermediate produced was hydrolyzed by cautious addition of 80 ml 6N HCl with ice cooling and vigorous stirring as the solution warmed to room temperature and then kept stirring at this temperature for 4 hrs. Solid sodium bicarbonate was added cautiously to neutralize the excess acid and the solid in the mixture was removed by vacuum filtration through a pad of Celite and the Celite pad was washed three more times with ethyl acetate. The filtrate was extracted three times with ethyl acetate, dried over anhydrous MgSO4. The solvent was removed by rotary evaporation and the product obtained as liquid, which was suitable for direct use in the next step. For further characterization one gram of the crude product was purified by silica gel column chromatography using EtOAc/hexane 1/4 as eluent. Calculated yield: (77%). 1H NMR (400 MHz, CDCl3) δ 7.88 (d, J=8.4 Hz, 2H), 7.49 (d, J=8.4 Hz, 2H), 4.01 (s, 1H), 1.51 (s, 6H). 13C NMR (100 MHz, (100 MHz, CDCl3) δ 203.21, 134.46, 132.63, 131.28, 127.68, 76.66, 28.11.

Workup

  1. customAn ice water bath was occasionally used
  2. customthe reaction
  3. additionAfter addition
  4. stirringwas stirred for 2 hrs
  5. stirringthe mixture was stirred for 20 hrs
  6. customBy this time a large quantity of white precipitate was formed
  7. customThe intermediate produced
  8. stirringvigorous stirring as the solution
  9. temperaturewarmed to room temperature
  10. stirringkept stirring at this temperature for 4 hrs
  11. customthe solid in the mixture was removed by vacuum filtration through a pad of Celite
  12. washthe Celite pad was washed three more times with ethyl acetate
  13. extractionThe filtrate was extracted three times with ethyl acetate
  14. dry with materialdried over anhydrous MgSO4
  15. customThe solvent was removed by rotary evaporation
  16. customthe product obtained as liquid, which
  17. customFor further characterization one gram of the crude product was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-f8b13c7cb04342ef99a4128d2af311a3
Source dataset
uspto-grants-2014_07
Patent number
US08772048B2

Reaction notes

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