Benzaldehyde → Donepezil

HRID 1881743Notes

Reaction equation

HRID 1881743 reaction equation
[C:1]1([CH3:11])[CH:6]=[CH:5][C:4](S(O)(=O)=O)=[CH:3][CH:2]=1.[CH3:12][O:13][C:14]1[CH:15]=[C:16]2[C:20](=[CH:21][C:22]=1[O:23][CH3:24])[C:19](=[O:25])[CH:18]([CH2:26][CH:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1)[CH2:17]2.C([O-])(=O)C.[Na+].C(=O)C1C=CC=CC=1>[Pd].CO>[CH3:12][O:13][C:14]1[CH:15]=[C:16]2[CH2:17][CH:18]([CH2:26][CH:27]3[CH2:32][CH2:31][N:30]([CH2:11][C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[CH2:29][CH2:28]3)[C:19](=[O:25])[C:20]2=[CH:21][C:22]=1[O:23][CH3:24]

Participants

6

Reactant 3

HCID 240BenzaldehydeHCID 517045Sodium AcetateHCID 86611641HCID 86611641, compound

Product 1

HCID 3152DonepezilYield 370.4%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

0.22 g of 2,3-dihydro-5,6-dimethoxy-2-((piperidin-4-yl)methyl)inden-1-one p-toluenesulfonic acid salt, and 0.10 g of sodium acetate were added to 60 mL of anhydrous methanol. 100 milligrams of 10% Pd/C were also added. The reaction mixture was stirred at room temperature with H2 being supplied at 1 atmosphere for 10 hours. 55 milligrams of benzaldehyde were added in equal portions at 0 hrs, 2 hrs, 4 hrs, 6 hrs and 8 hrs. Solids were filtered off. The filtrate was concentrated. 30 mL of 5% aqueous Na2CO3 solution were added, and the resulting mixture was extracted with 3×30 mL of ethyl acetate. The extracts were combined, washed with 15 mL of aqueous Na2CO3 solution and 15 mL of aqueous NaCl solution, and dried over anhydrous MgSO4. After solids were filtered off, solvent was removed in vacuo to afford 0.67 g of product as oil. Purification on silica gel column chromatography afforded 0.11 g of title compound in 62% yield.

Workup

  1. filtrationSolids were filtered off
  2. concentrationThe filtrate was concentrated
  3. addition30 mL of 5% aqueous Na2CO3 solution were added
  4. extractionthe resulting mixture was extracted with 3×30 mL of ethyl acetate
  5. washwashed with 15 mL of aqueous Na2CO3 solution and 15 mL of aqueous NaCl solution
  6. dry with materialdried over anhydrous MgSO4
  7. filtrationAfter solids were filtered off
  8. customsolvent was removed in vacuo

Sources & evidence

ORD record
ord-5a2ad838d0e04d0894eaff47615b7e5a
Source dataset
uspto-grants-2012_11
Patent number
US08318942B2

Reaction notes

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