Acetic Acid → 2-[2-(1-Methoxy-2-methyl-2,3-dihydro-1H-inden-4-yl)ethyl]indan-2-ol

HRID 1047470Notes

Reaction equation

HRID 1047470 reaction equation
[Mg].Br[CH2:3][CH2:4][C:5]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:6]=1[CH2:7][CH:8]([CH3:16])[CH:9]2[O:14][CH3:15].[C:17]([OH:20])(=O)[CH3:18]>C1COCC1>[CH3:15][O:14][CH:9]1[C:10]2[C:6](=[C:5]([CH2:4][CH2:3][C:17]3([OH:20])[CH2:18][C:13]4[C:5](=[CH:6][CH:10]=[CH:11][CH:12]=4)[CH2:4]3)[CH:13]=[CH:12][CH:11]=2)[CH2:7][CH:8]1[CH3:16]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 5462224MagnesiumHCID 584187554-(2-Bromoethyl)-1-methoxy-2-methylindane

Product 1

HCID 596089132-[2-(1-Methoxy-2-methyl-2,3-dihydro-1H-inden-4-yl)ethyl]indan-2-ol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To 2.26 g (93.0 mmol) of magnesium turnings in 20 ml of THF a solution of 16.7 g (62.0 mmol) of 4-(2-bromoethyl)-1-methoxy-2-methylindane in 80 ml of THF was added dropwise at reflux. The resulting mixture was additionally refluxed for 1 h, and then this Grignard reagent was titrated. To a suspension of 10.9 g (44.1 mmol) of anhydrous CeCl3 in 160 ml of THF 100 ml (44.1 mmol) of 0.441 M solution of the Grignard reagent was added at vigorous stirring for 15 min at 0° C., and then the reaction mixture was stirred at this temperature for 1.5 h. Further on, 5.83 g (44.1 mmol) of indanone-2 was added at 0° C. This mixture was stirred overnight at room temperature, and then 300 ml of 10% acetic acid was added. The product was extracted by 3×100 ml of ether. The combined extract was washed by brain and aqueous Na2CO3. The organic layer was separated, dried over Na2SO4, and evaporated to dryness. The title product was isolated by flash chromatography on Silica Gel 60 (40-63 um, d 50 mm, l 300 mm, eluent: hexanes/ether=3/1). Yield 10.7 g (75%) of a one diastereomer (as the starting material was one pure diastereomer).

Workup

  1. temperatureat reflux
  2. temperatureThe resulting mixture was additionally refluxed for 1 h
  3. additionwas added
  4. stirringthe reaction mixture was stirred at this temperature for 1.5 h
  5. stirringThis mixture was stirred overnight at room temperature
  6. extractionThe product was extracted by 3×100 ml of ether
  7. extractionThe combined extract
  8. washwas washed by brain and aqueous Na2CO3
  9. customThe organic layer was separated
  10. dry with materialdried over Na2SO4
  11. customevaporated to dryness

Sources & evidence

ORD record
ord-f8dbdcf85c0c497981f604030bbf3fc1
Source dataset
uspto-grants-2013_10
Patent number
US08569532B2

Reaction notes

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