Sulfuric Acid → 1-(4-Methylenecyclohexyl)-2-[4-(2-methylquinolin-4-ylmethoxy)benzenesulfonyl]ethanone

HRID 1788363Notes

Reaction equation

HRID 1788363 reaction equation
[CH:1]([N-:4]C(C)C)(C)[CH3:2].[Li+].[CH2:9]=[C:10]1[CH2:15][CH2:14][CH:13]([C:16]([O:18]C)=O)[CH2:12][CH2:11]1.[S:20](=[O:24])(=O)(O)[OH:21].[C:25](=[O:28])(O)[O-].[Na+].[CH3:30][CH2:31][CH2:32][CH2:33][CH2:34][CH3:35].[CH3:36]CCCCCC.[CH2:43]([C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)[CH3:44]>O1CCCC1>[CH2:9]=[C:10]1[CH2:11][CH2:12][CH:13]([C:16](=[O:18])[CH2:36][S:20]([C:32]2[CH:31]=[CH:30][C:35]([O:28][CH2:25][C:43]3[C:45]4[C:50](=[CH:49][CH:48]=[CH:47][CH:46]=4)[N:4]=[C:1]([CH3:2])[CH:44]=3)=[CH:34][CH:33]=2)(=[O:24])=[O:21])[CH2:14][CH2:15]1

Participants

7

Reactant 5

HCID 1118Sulfuric AcidHCID 516892Sodium BicarbonateHCID 2724682Lithium diisopropylamideHCID 10796960Methyl 4-methylenecyclohexanecarboxylateHCID 86595268Hexane heptane ethylbenzene

Product 1

HCID 688263631-(4-Methylenecyclohexyl)-2-[4-(2-methylquinolin-4-ylmethoxy)benzenesulfonyl]ethanoneYield 60%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Into a solution of 1.95 g (5.94 mmol) of 4-(4-methanesulfonylphenoxymethyl)-2-methylquinoline (VI-1) obtained in the above (1-1) in tetrahydrofuran (150 mL) was dropped 3.7 mL (7.43 mmol) of 2 mol/L lithium diisopropylamide solution in hexane-heptane-ethylbenzene (available from Aldrich) at −78° C. under an atmosphere of argon, followed by stirring for 1 hour. Into this solution, a solution of 1.1 g (6.54 mmol) of methyl 4-methylenecyclohexane carboxylate in tetrahydrofuran (5 mL) was dropped at −78° C., and then stirred for 4 hours. After 1 N sulfuric acid (4 mL) was added to the reaction mixture and stirred for 10 minutes, the solution was neutralized with saturated aqueous sodium bicarbonate. The reaction mixture was concentrated under a reduced pressure, and the residue was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and followed by evaporation of the solvent. The obtained residue was purified by column chromatography (silica gel 50 g, developing solvent: hexane:ethyl acetate=1:3) to give 1.67 g (yield 60.0%) of 1-(4-methylenecyclohexyl)-2-[4-(2-methylquinolin-4-ylmethoxy)benzenesulfonyl]ethanone (X-1) as a colorless crystal. Its physical properties are shown below.

Workup

  1. stirringstirred for 4 hours
  2. stirringstirred for 10 minutes
  3. concentrationThe reaction mixture was concentrated under a reduced pressure
  4. extractionthe residue was extracted with ethyl acetate
  5. washThe organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customfollowed by evaporation of the solvent
  8. customThe obtained residue was purified by column chromatography (silica gel 50 g, developing solvent: hexane:ethyl acetate=1:3)

Sources & evidence

ORD record
ord-1f594dc67e90472b9b1290cb3a5d457c
Source dataset
uspto-grants-2009_03
Patent number
US07511144B2

Reaction notes

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