Bromoform → Methyl 2-(benzo[d][1,3]dioxol-5-yl)-2-hydroxyacetate

HRID 1934610Notes

Reaction equation

HRID 1934610 reaction equation
[Cl-].[Li+].[OH-:3].[K+].[CH:5]1[C:10]([CH:11]=[O:12])=[CH:9][C:8]2[O:13][CH2:14][O:15][C:7]=2[CH:6]=1.C(Br)(Br)Br.O1C[CH2:24][O:23][CH2:22]C1>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O.CO.S(=O)(=O)(O)O>[O:15]1[C:7]2[CH:6]=[CH:5][C:10]([CH:11]([OH:12])[C:24]([O:23][CH3:22])=[O:3])=[CH:9][C:8]=2[O:13][CH2:14]1

Participants

10

Reactant 5

HCID 5558BromoformHCID 8438PiperonalHCID 14797Potassium HydroxideHCID 312751,4-DioxaneHCID 433294Lithium Chloride

Product 1

HCID 273389Methyl 2-(benzo[d][1,3]dioxol-5-yl)-2-hydroxyacetate

Reagents, catalysts & solvents 4

HCID 1118Sulfuric AcidCatalystHCID 74236Tetrabutylammonium BromideCatalystHCID 887MethanolSolventHCID 962WaterSolvent2×

Procedure

Lithium chloride (11.8 g), potassium hydroxide (31.4 g) and tetrabutylammonium bromide (4.5 g) were dissolved in a mixture of 1,4-dioxane (120 ml) and water (120 ml). Piperonal (21 g, 140 mmol) was added to this vigorously stirred ice-cold mixture, and after 10 minutes bromoform (12.2 ml 140 mmol) was added dropwise over ˜30 minutes. Stirring was continued for 20 hours at ambient temperature. Water (500 ml) was added and the mixture warmed to dissolve the precipitate. After washing with diethylether, the aqueous solution was acidified with concentrated hydrochloric acid. The crude carboxylic acid intermediate was isolated by extraction with diethylether and evaporation in vacuo. The residue was dissolved in methanol (500 ml) and acidified with 20 drops of concentrated sulphuric acid. The solution was heated to reflux for 2 hours, then cooled and evaporated in vacuo. The residue was dissolved in diethylether and washed with water. The organic fraction was dried (magnesium sulphate), and concentrated in vacuo. Flash chromatography using dichloromethane as eluant, and then recrystallisation from diisopropylether gave 13.2 g of the subtitle compound. (m.p. 93-95° C.)

Workup

  1. temperaturethe mixture warmed
  2. dissolutionto dissolve the precipitate
  3. washAfter washing with diethylether
  4. customThe crude carboxylic acid intermediate was isolated by extraction with diethylether and evaporation in vacuo
  5. temperatureThe solution was heated
  6. temperatureto reflux for 2 hours
  7. temperaturecooled
  8. customevaporated in vacuo
  9. dissolutionThe residue was dissolved in diethylether
  10. washwashed with water
  11. dry with materialThe organic fraction was dried (magnesium sulphate)
  12. concentrationconcentrated in vacuo
  13. customrecrystallisation from diisopropylether

Sources & evidence

ORD record
ord-fd2027222e444febb609469decbf44eb
Source dataset
uspto-grants-2002_05
Patent number
US06384070B2

Reaction notes

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