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

HRID 537000Notes

Reaction equation

HRID 537000 reaction equation
CC1C=CC(S([CH2:11][N+:12]#[C-])(=O)=O)=CC=1.CC(C)([O-])C.[K+].[CH3:20][O:21][C:22]1[CH:23]=[C:24]2[C:27](=[CH:28][C:29]=1[O:30][CH3:31])[C:26](=O)[CH2:25]2.[Br-].[Li+].Cl>C1COCC1.O.CO>[CH3:20][O:21][C:22]1[CH:23]=[C:24]2[C:27](=[CH:28][C:29]=1[O:30][CH3:31])[CH:26]([C:11]#[N:12])[CH2:25]2

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 82050Lithium BromideHCID 161915Tosylmethyl isocyanide2×HCID 27527583,4-Dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-oneHCID 23665647Potassium tert-butoxide2×

Product 1

HCID 2905443,4-Dimethoxybicyclo[4.2.0]octa-1,3,5-triene-7-carbonitrileYield 54%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

A solution of TosMIC (0.98 g, 4.98 mmol, 2.3 eq) in THF (3 mL) is poured, over 20 minutes, into a solution of potassium tert-butoxide (1.22 g; 10.9 mmol; 5 eq) in THF (7.5 mL) stirred at 0° C. under nitrogen. Then 200 μL of methanol are added to the mixture and stirring is maintained for 30 minutes at 0° C. In parallel, 3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-one (0.39 g, 2.17 mmol, 1 eq), lithium bromide (0.19 g, 2.17 mmol, 1 eq) and THF (2.5 mL) are transferred into a second three-necked flask. After cooling to 0° C. under nitrogen, the solution of TosMIC and potassium tert-butoxide is transferred to the reaction mixture. After returning to ambient temperature, the solution is heated to 40° C. and stirred for 16 hours at that temperature. The mixture is then hydrolysed with a solution of 11N HCl (0.7 mL, 7.73 mmol) in water (2 mL). After evaporating off the THF under reduced pressure, the product is extracted with 5 mL of dichloromethane. The organic phase is washed twice with 2×5 mL of water before being dried. The crude product is purified by column chromatography over silica gel using the binary mixture methylcyclohexane/ethyl acetate 75/25 to obtain the title product in the form of a cream-coloured powder.

Workup

  1. stirringstirring
  2. temperatureis maintained for 30 minutes at 0° C
  3. temperatureAfter cooling to 0° C. under nitrogen
  4. customAfter returning to ambient temperature
  5. temperaturethe solution is heated to 40° C.
  6. stirringstirred for 16 hours at that temperature
  7. customAfter evaporating off the THF under reduced pressure
  8. extractionthe product is extracted with 5 mL of dichloromethane
  9. washThe organic phase is washed twice with 2×5 mL of water
  10. custombefore being dried
  11. customThe crude product is purified by column chromatography over silica gel using the binary mixture methylcyclohexane/ethyl acetate 75/25

Sources & evidence

ORD record
ord-86835fb9868b43f184290a0b980aea1c
Source dataset
uspto-grants-2014_10
Patent number
US08859763B1

Reaction notes

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