2,2-Dimethoxypropane → 7-(2,2-Dimethyl-1,3-dioxolan-4-yl)chroman-4-one

HRID 1506425Notes

Reaction equation

HRID 1506425 reaction equation
[OH:1][CH:2]([C:5]1[CH:14]=[C:13]2[C:8]([C:9](=[O:15])[CH2:10][CH2:11][O:12]2)=[CH:7][CH:6]=1)[CH2:3][OH:4].CO[C:18](OC)([CH3:20])[CH3:19].[C@@]12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>CC(C)=O>[CH3:19][C:18]1([CH3:20])[O:1][CH:2]([C:5]2[CH:14]=[C:13]3[C:8]([C:9](=[O:15])[CH2:10][CH2:11][O:12]3)=[CH:7][CH:6]=2)[CH2:3][O:4]1

Participants

5

Reactant 3

HCID 64952,2-DimethoxypropaneHCID 131278(R)-camphorsulfonic acidHCID 671711277-(1,2-Dihydroxyethyl)chroman-4-one

Product 1

HCID 671721797-(2,2-Dimethyl-1,3-dioxolan-4-yl)chroman-4-oneYield 58.1%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a mixture of 7-(1,2-dihydroxyethyl)chroman-4-one (Preparation 60A, 0.950 g, 4.56 mmol) and 2,2-dimethoxypropane (1.68 mL, 13.7 mmol) in acetone (20 mL) at room temperature was added (1R)-(−)-camphorsulfonic acid (0.212 g, 0.913 mmol). The reaction mixture was stirred at room temperature overnight. The reaction mixture was quenched with a saturated aqueous solution of sodium bicarbonate and concentrated under reduced pressure. The aqueous residue was diluted with ethyl acetate, washed with a saturated aqueous solution of sodium bicarbonate, and brine. The organic layer was collected, and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate and concentrated to give the crude product as a dark oil, which was purified by flash silica gel chromatography using a 20% mixture of ethyl acetate and hexane to afford 7-(2,2-dimethyl-1,3-dioxolan-4-yl)chroman-4-one (0.657 g, 2.65 mmol, 58% yield) as a clear, colorless oil. The product had an HPLC ret. time=2.14 min.−Column: Chromolith SpeedROD 4.6×50 mm (4 min.); Solvent A=10% MeOH, 90% H2O, 0.1% TFA; Solvent B=90% MeOH, 10% H2O, 0.1% TFA. LC/MS M+1=248.9.

Workup

  1. customThe reaction mixture was quenched with a saturated aqueous solution of sodium bicarbonate
  2. concentrationconcentrated under reduced pressure
  3. additionThe aqueous residue was diluted with ethyl acetate
  4. washwashed with a saturated aqueous solution of sodium bicarbonate, and brine
  5. customThe organic layer was collected
  6. extractionthe aqueous layer was extracted with ethyl acetate
  7. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  8. concentrationconcentrated
  9. customto give the crude product as a dark oil, which
  10. customwas purified by flash silica gel chromatography

Sources & evidence

ORD record
ord-6d3f88d320e04f91b375974b506ca83b
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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