Ethanol → 2,3-Dihydro-1,4-benzodioxin-5-acetic acid

HRID 2297568Notes

Reaction equation

HRID 2297568 reaction equation
O[CH2:2][C:3]1[C:12]2[O:11][CH2:10][CH2:9][O:8][C:7]=2[CH:6]=[CH:5][CH:4]=1.S(Cl)(Cl)=O.[C-]#N.[Na+].[OH-:20].[Na+].[CH2:22]([OH:24])C>ClCCl.O.CN(C)C=O>[O:8]1[C:7]2[CH:6]=[CH:5][CH:4]=[C:3]([CH2:2][C:22]([OH:24])=[O:20])[C:12]=2[O:11][CH2:10][CH2:9]1

Participants

9

Reactant 5

HCID 702EthanolHCID 8929Sodium CyanideHCID 14798Sodium HydroxideHCID 24386Thionyl ChlorideHCID 27761822,3-dihydro-1,4-benzodioxin-5-ylmethanol

Product 1

HCID 183823762,3-Dihydro-1,4-benzodioxin-5-acetic acidYield 43%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-hydroxymethyl-1,4-benzodioxan (8.0 g, 48 mmol) in dichloromethane (200 mL) was added two droplets of N,N-dimethylformamide and thionyl chloride (5.0 mL, 68 mmol) at room temperature. After the resulting solution was boiled under reflux for 1 h and subsequently cooled to room temperature water (100 mL) was added. The phases were separated and the organic phase was dried (MgSO4) and the solvents evaporated in vacuo. A solution of the remaining oil (8.5 g, 46 mmol) was added to a mixture of sodium cyanide (5.0 g, 102 mmol) and N,N-dimethylformamide (100 mL) at room temperature. After stirring for 16 h at room temperature ice was added and the resulting slurry was extracted with diethyl ether (2×250 mL). The collected organic phases were washed with saturated calcium chloride, dried (Na2SO4) and the solvents were evaporated in vacuo. A mixture of the remaining oil (6.0 g, 34 mmol), ethanol (200 mL), sodium hydroxide (6.0 g) and water (6 mL) was boiled under reflux for 16 h. After evaporation of the solvents in vacuo, water (200 mL) was added and the resulting slurry was extracted with diethyl ether (2×200 mL). The collected organic phases were washed with brine, dried (Na2SO4) and the solvents were evaporated in vacuo affording 4.0 g (43%) of the title compound as an oil: 1H NMR (CDCl3) δ 3.65 (s, 2H), 4.15-4.30 (m, 4H), 6.70-6.85 (m, 3H).

Workup

  1. temperatureunder reflux for 1 h
  2. additionwas added
  3. customThe phases were separated
  4. dry with materialthe organic phase was dried (MgSO4)
  5. customthe solvents evaporated in vacuo
  6. additionwas added
  7. extractionthe resulting slurry was extracted with diethyl ether (2×250 mL)
  8. washThe collected organic phases were washed with saturated calcium chloride
  9. dry with materialdried (Na2SO4)
  10. customthe solvents were evaporated in vacuo
  11. temperatureunder reflux for 16 h
  12. customAfter evaporation of the solvents in vacuo, water (200 mL)
  13. additionwas added
  14. extractionthe resulting slurry was extracted with diethyl ether (2×200 mL)
  15. washThe collected organic phases were washed with brine
  16. dry with materialdried (Na2SO4)
  17. customthe solvents were evaporated in vacuo

Sources & evidence

ORD record
ord-c6379377236640c69bff818355774ccc
Source dataset
uspto-grants-2002_12
Patent number
US06492374B2

Reaction notes

Loading…