Methyl vinyl ketone → 2-Butyl-5-methoxy-4-methyl-2-(3-oxo-butyl)-1-indanone

HRID 7847

Reaction equation

HRID 7847 reaction equation
[CH:1]([C:3]([CH3:5])=[O:4])=[CH2:2].N12CCCN=C1CCCCC2.[CH2:17]([CH:21]1[CH2:29][C:28]2[C:23](=[CH:24][CH:25]=[C:26]([O:31][CH3:32])[C:27]=2[CH3:30])[C:22]1=[O:33])[CH2:18][CH2:19][CH3:20]>O1CCCC1.CCOCC>[CH2:17]([C:21]1([CH2:2][CH2:1][C:3](=[O:4])[CH3:5])[CH2:29][C:28]2[C:23](=[CH:24][CH:25]=[C:26]([O:31][CH3:32])[C:27]=2[CH3:30])[C:22]1=[O:33])[CH2:18][CH2:19][CH3:20]

Participants

6

Reactant 3

HCID 6570Methyl vinyl ketoneHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 219908832-Butyl-5-methoxy-4-methyl-1-indanone

Product 1

HCID 219908922-Butyl-5-methoxy-4-methyl-2-(3-oxo-butyl)-1-indanoneYield 81.4%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

Methyl vinyl ketone (MVK, 0.49 mL, 5.9 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 0.12 mL, 0.8 mmol) were added to a solution of impure 2-butyl-5-methoxy-4-methyl-1-indanone (0.90 g, 3.9 mmol) in anhydrous tetrahydrofuran (THF, 3.9 mL). The resulting solution was stirred at room temperature for 30 hours, then diluted with Et2O (50 mL), washed with water (20 mL), 1N HCl (20 mL), and brine (20 mL), dried over MgSO4, filtered, and evaporated under vacuum to an amber oil (1.23 g). The crude product was purified by chromatography on EM silica gel 60 (230-400 mesh, 125 mL dry, packed under 4:1 hexanes-EtOAc). The column was eluted with 4:1 hexanes-EtOAc, collecting 25 mL fractions. Fractions 14-27 gave a 93:2:5 mixture (0.96 g) of 2-butyl-5-methoxy-4-methyl-2-(3-oxo-butyl)-1-indanone, the 6-methyl isomer, and the desmethyl product. This material was used in the next step.

Workup

  1. washwashed with water (20 mL), 1N HCl (20 mL), and brine (20 mL)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. customevaporated under vacuum to an amber oil (1.23 g)
  5. customThe crude product was purified by chromatography on EM silica gel 60 (230-400 mesh, 125 mL dry, packed under 4:1 hexanes-EtOAc)
  6. washThe column was eluted with 4:1 hexanes-EtOAc
  7. customcollecting 25 mL fractions

Sources & evidence

ORD record
ord-2a4993889ca6480cb0bfdfaca22cc970
Source dataset
uspto-grants-2006_08
Patent number
US07087599B2

Linked notes

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