ChemicalBook CAS DataBase List Donepezil

Donepezil synthesis

7synthesis methods

Product Name:Donepezil
CAS Number:120014-06-4
Molecular formula:C24H29NO3
Molecular Weight:379.49

2107-69-9 Synthesis

2107-69-9
512 suppliers
$6.00/5g

67686-01-5
141 suppliers
$14.00/1g

120014-06-4
333 suppliers
$5.00/100mg

Yield:120014-06-4 98%

Reaction Conditions:

with C₁₈H₂₃ClFIrN₃⁽¹⁺⁾*Cl^(1-);potassium hydroxide in lithium hydroxide monohydrate;toluene at 100; for 16 h;Catalytic behavior;Inert atmosphere;Schlenk technique;Large scale;Reagent/catalyst;Solvent;

Steps:

General Procedure for Synthesis of ketones

General procedure: A mixture of 1 (0.55 mmol), 2 (0.5mmol), KOH (0.55 mmol), toluene/H2O (3.0 mL, 10:1), and TC-3 (0.5 mol%) were added into a 10.0 mL Schlenk tube under N2 atmosphere, which was reacted at 100oC for 16 h. After completion, the mixture was extracted with ethyl acetate (3 5.0 mL), dried over magnesium sulfate and concentrated in vacuum, which was purified by silica gel chromatography using a mixture of EtOAc/petroleum ether (1/50~5:1) as eluent to afford the ketone products. General Procedure for Scale-up of donepezil 3aA mixture of 1a (6.0 mmol), 2a (5.0 mmol), KOH (5.5 mmol),toluene/H2O (15.0 mL, 10:1), and TC-3 (0.5 mol%) were added into a100.0 mL Schlenk tube under N2 atmosphere, which was reacted at100oC for 16h. After completion, the mixture was extracted with ethylacetate (3 × 10.0 mL), dried over magnesium sulfate and concentrated invacuum, which was purified by silica gel chromatography using amixture of DCM/MeOH/HCO2H (80/2/1) as eluent to afford thedonepezil 3a.2-((1-benzylpiperidin-4-yl)methyl)-5,6-dimetho-xy-2,3-dihydro-1H-inden-1-one (3a) 28Yield: 3671.4 mg (98%), white solid (mp: 220-222°C).¹H NMR (400 MHz, CDCl₃) δ 7.30 (t, J = 6.8 Hz, 4H), 7.27-7.21 (m, 1H),7.16 (s, 1H), 6.85 (s, 1H), 3.95 (s, 3H), 3.89 (s, 3H), 3.50 (s, 2H), 3.22 (dd, J= 17.5, 8.1 Hz, 1H), 2.90 (t, J = 9.2 Hz, 2H), 2.70 (dd, J = 12.0, 5.1 Hz, 2H),2.02-1.86 (m, 3H), 1.70 (dd, J = 30.1, 12.5 Hz, 2H), 1.55-1.43 (m, 1H), 1.34(tdd, J = 13.2, 11.0, 4.6 Hz, 3H).¹³C NMR (100 MHz, CDCl₃) δ 207.9, 155.4, 149.4, 148.8, 138.4, 129.3,129.3, 128.1, 126.9, 107.4, 104.3, 63.5, 56.2, 56.1, 53.8, 53.8, 45.5, 38.7,34.5, 33.3, 33.1, 31.8.

References:

Wang, Sen;Miao, Rui;Xia, Yanping;Wei, Yifei;Luo, Renshi;Ouyang, Lu [Synthesis,2022,vol. 54,# 23,p. 5253 - 5260]