Toluene → Ethyl α-hydroxy-6-(methoxymethoxy)-7-methyl-1,3-benzodioxole-4-acetate

HRID 587911Notes

Reaction equation

HRID 587911 reaction equation
[OH:1][C:2]1[C:7]([OH:8])=[C:6]([CH3:9])[C:5]([O:10][CH2:11][O:12][CH3:13])=[CH:4][C:3]=1[CH:14]([OH:20])[C:15]([O:17][CH2:18][CH3:19])=[O:16].[C:21]1(C)C=CC=CC=1>CN(C=O)C>[OH:20][CH:14]([C:3]1[C:2]2[O:1][CH2:21][O:8][C:7]=2[C:6]([CH3:9])=[C:5]([O:10][CH2:11][O:12][CH3:13])[CH:4]=1)[C:15]([O:17][CH2:18][CH3:19])=[O:16]

Participants

4

Reactant 2

HCID 1140TolueneHCID 118037693HCID 118037693, compound

Product 1

HCID 11702123Ethyl α-hydroxy-6-(methoxymethoxy)-7-methyl-1,3-benzodioxole-4-acetate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Into a clean and dry 2 L, 4-necked RB flask was charged 400 ml of N,N-dimethylformamide under nitrogen atmosphere at RT. Cesium carbonate (171 g) was added to the reaction mass under stirring at room temperature. Bromochloromethane (226 g) was added to the reaction mass under stirring at RT. Reaction mass was heated to 30-35° C. Ethyl 2-(2,3-dihydroxy-5-(methoxymethoxy)-4-methylphenyl)-2-hydroxyacetate (50 g) was dissolved in 100 ml of DMF and slowly added to the reaction mass under stirring at 30-35° C. Reaction mass was maintained at 30-35° C. for 2.5 h under stirring. Reaction mass was poured into 1 L toluene and stirred for 1.0 h at RT. Reaction mass was filtered through hyflow bed, and the bed washed with 600 mL of toluene. Filtrate was washed with 2.0 L of DM water. Aqueous layer was extracted with 2×500 mL of toluene. Combined organic layer was washed with 2×600 mL of saturated sodium chloride solution and treated with 7.5 g of activated carbon at 45-50° C. Reaction mass was filtered and distilled of solvent under vacuum at 45-55° C. to get 40 g of crude title compound as syrup. HPLC purity of the crude compound is 92.5%. The crude compound was directly used in next step. A small sample was purified by column chromatography to compare its spectral data with the literature values.

Workup

  1. customInto a clean and dry 2 L, 4-necked RB flask
  2. additionwas charged 400 ml of N,N-dimethylformamide under nitrogen atmosphere at RT
  3. additionCesium carbonate (171 g) was added to the reaction mass
  4. additionBromochloromethane (226 g) was added to the reaction mass
  5. stirringunder stirring at RT
  6. customReaction mass
  7. temperaturewas heated to 30-35° C
  8. additionslowly added to the reaction mass
  9. stirringunder stirring at 30-35° C
  10. customReaction mass
  11. temperaturewas maintained at 30-35° C. for 2.5 h
  12. stirringunder stirring
  13. customReaction mass
  14. stirringstirred for 1.0 h at RT
  15. customReaction mass
  16. filtrationwas filtered through hyflow bed
  17. washthe bed washed with 600 mL of toluene
  18. washFiltrate was washed with 2.0 L of DM water
  19. extractionAqueous layer was extracted with 2×500 mL of toluene
  20. washCombined organic layer was washed with 2×600 mL of saturated sodium chloride solution
  21. additiontreated with 7.5 g of activated carbon at 45-50° C
  22. customReaction mass
  23. filtrationwas filtered
  24. distillationdistilled of solvent under vacuum at 45-55° C.

Sources & evidence

ORD record
ord-27f9ff820cc148b2805b5baa0af73c7b
Source dataset
uspto-grants-2016_01
Patent number
US09227948B2

Reaction notes

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