Water → 3,4-Dimethoxybicyclo[4.2.0]octa-1,3,5-triene-7-carbonitrile

HRID 420867Notes

Reaction equation

HRID 420867 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.CN(C)S(=O)(=O)O[C:17]1[CH:22]=[C:21]([O:23][CH3:24])[C:20]([O:25][CH3:26])=[CH:19][C:18]=1[CH2:27][CH2:28][C:29]#[N:30].O>CCCCCC.C1COCC1>[CH3:26][O:25][C:20]1[CH:19]=[C:18]2[C:17](=[CH:22][C:21]=1[O:23][CH3:24])[CH:28]([C:29]#[N:30])[CH2:27]2

Participants

7

Reactant 4

HCID 962WaterHCID 7912DiisopropylamineHCID 666574992-(2-Cyanoethyl)-4,5-dimethoxyphenyl dimethylsulphamateHCID 178418339Butyllithium

Product 1

HCID 2905443,4-Dimethoxybicyclo[4.2.0]octa-1,3,5-triene-7-carbonitrileYield 110.8%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-50 °C

Procedure

Under nitrogen, mix together 5.4 ml (0.0382 mol) of redistilled diisopropylamine and 60 ml of THF. Cool the mixture to −50° C. and pour in dropwise 15.3 ml (0.0382 mol) of a 2.5N solution of butyllithium in hexane. Allow the temperature to rise again to −5° C. and stir for 10 minutes. Cool the solution to −60° C. and pour in dropwise a solution of 3 g (0.00954 mol) of 2-(2-cyanoethyl)-4,5-dimethoxyphenyl dimethylsulphamate in 35 ml of THF. Allow the temperature slowly to rise again to −24° C. while monitoring by HPLC disappearance of the reactant. Add the reaction mixture to a mixture of water and ice and extract with ethyl acetate. Wash the organic phases in succession with 1N sodium hydroxide solution, aqueous 1N HCl solution, water and saturated aqueous NaCl solution and then dry them over MgSO4, filter, and evaporate off the solvents. 2 g of residue are obtained which is purified by flash chromatography on 70 g of silica (eluant=dichloromethane) to yield 0.9 g of title product in the form of a white solid.

Workup

  1. customto rise again to −5° C.
  2. temperatureCool the solution to −60° C.
  3. customto rise again to −24° C. while monitoring by HPLC disappearance of the reactant
  4. additionAdd the reaction mixture
  5. extractionextract with ethyl acetate
  6. washWash the organic phases in succession with 1N sodium hydroxide solution, aqueous 1N HCl solution, water and saturated aqueous NaCl solution
  7. dry with materialdry them over MgSO4
  8. filtrationfilter
  9. customevaporate off the solvents

Sources & evidence

ORD record
ord-8df38abecf3448278950b0a677c5e602
Source dataset
uspto-grants-2012_01
Patent number
US08097720B2

Reaction notes

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