Sulfuric Acid → alpha-(2,5-dimethoxy-3,4,6-trimethylphenyl)-2,2,4-(S)-trimethyl-1,3-dioxolan-4-ethanol

HRID 262059Notes

Reaction equation

HRID 262059 reaction equation
[Mg].CI.Br[C:5]1[C:10]([CH3:11])=[C:9]([O:12][CH3:13])[C:8]([CH3:14])=[C:7]([CH3:15])[C:6]=1[O:16][CH3:17].[CH3:18][C:19]1([CH3:28])[O:23][C@@:22]([CH3:27])([CH2:24][CH:25]=[O:26])[CH2:21][O:20]1.[Cl-].[NH4+].S(=O)(=O)(O)O>O1CCCC1>[CH3:17][O:16][C:6]1[C:7]([CH3:15])=[C:8]([CH3:14])[C:9]([O:12][CH3:13])=[C:10]([CH3:11])[C:5]=1[CH:25]([OH:26])[CH2:24][C@@:22]1([CH3:27])[CH2:21][O:20][C:19]([CH3:18])([CH3:28])[O:23]1

Participants

8

Reactant 6

HCID 1118Sulfuric AcidHCID 6328Methyl iodideHCID 25517Ammonium ChlorideHCID 2973651-Bromo-2,5-dimethoxy-3,4,6-trimethylbenzeneHCID 5462224MagnesiumHCID 53704870[(4S)-2,2,4-Trimethyl-1,3-dioxolan-4-yl]acetaldehyde

Product 1

HCID 22807699alpha-(2,5-dimethoxy-3,4,6-trimethylphenyl)-2,2,4-(S)-trimethyl-1,3-dioxolan-4-ethanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To 0.8 g of magnesium shavings activated with methyl iodide was added dropwise a solution of 7.77 g of 1-bromo-2,5-dimethoxy-3,4,6-trimethylbenzene in 20 ml of absolute tetrahydrofuran at a rate such that the solvent was brought just to boiling. Subsequently, the reaction mixture was boiled under reflux for an additional hour. To this Grignard solution, cooled down to 0°, were added dropwise 5.0 g of (S)-2,2,4-trimethyl-1,3-dioxolan-4-acetaldehyde. Subsequently, the reaction mixture was stirred at room temperature for a further 4 hours and under reflux for 15 minutes. For the working-up, the reaction mixture was cooled down to 0°, it was treated with 10 ml of saturated ammonium chloride solution followed by 10 ml of 2-N sulfuric acid and extracted with a total of 0.51 of ether. The organic phase was washed neutral with water and dried over magnesium sulfate. After removal of the solvent on a rotary evaporator and drying of the residue in a high vacuum, there were obtained 10.5 g of a highly viscous oil, which, for purification, was chromatographed on 450 g of Kieselgel with ether/hexane/acetic ester (4:4:1 parts by volume). The yield of α-(2,5-dimethoxy-3,4,6-trimethylphenyl)-2,2,4-(S)-trimethyl-1,3-dioxolan-4-ethanol amounted to 8.83 g; [α]D20 =-5.5° (c=1.20; CHCl3).

Workup

  1. temperatureunder reflux for an additional hour
  2. temperatureTo this Grignard solution, cooled down to 0°
  3. temperatureunder reflux for 15 minutes
  4. temperaturethe reaction mixture was cooled down to 0°
  5. extractionextracted with a total of 0.51 of ether
  6. washThe organic phase was washed neutral with water
  7. dry with materialdried over magnesium sulfate
  8. customAfter removal of the solvent
  9. customon a rotary evaporator
  10. customdrying of the residue in a high vacuum
  11. customthere were obtained 10.5 g of a highly viscous oil, which
  12. customfor purification
  13. customwas chromatographed on 450 g of Kieselgel with ether/hexane/acetic ester (4:4:1 parts by volume)
  14. custom[α]D20 =-5.5° (c=1.20; CHCl3)

Sources & evidence

ORD record
ord-86a44868c0f4431e8403e239aba13ab4
Source dataset
uspto-grants-1979_05
Patent number
US04153614

Reaction notes

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