2-Butenoic acid, 3-amino-, ethyl ester, (2Z)- → Amlodipine 2-Phthalimide

HRID 25478

Reaction equation

HRID 25478 reaction equation
[Cl:1][C:2]1[CH:31]=[CH:30][CH:29]=[CH:28][C:3]=1[CH:4]=[C:5]([C:11]([CH2:13][O:14][CH2:15][CH2:16][N:17]1[C:21](=[O:22])[C:20]2=[CH:23][CH:24]=[CH:25][CH:26]=[C:19]2[C:18]1=[O:27])=O)[C:6]([O:8][CH2:9][CH3:10])=[O:7].[CH2:32]([O:34][C:35](=[O:40])/[CH:36]=[C:37](\[NH2:39])/[CH3:38])[CH3:33]>CC(O)C>[Cl:1][C:2]1[CH:31]=[CH:30][CH:29]=[CH:28][C:3]=1[CH:4]1[C:36]([C:35]([O:34][CH2:32][CH3:33])=[O:40])=[C:37]([CH3:38])[NH:39][C:11]([CH2:13][O:14][CH2:15][CH2:16][N:17]2[C:21](=[O:22])[C:20]3[C:19](=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:18]2=[O:27])=[C:5]1[C:6]([O:8][CH2:9][CH3:10])=[O:7]

Participants

4

Reactant 2

HCID 6437562-Butenoic acid, 3-amino-, ethyl ester, (2Z)-HCID 53879087Ethyl 2-(2-chlorobenzylidene)-4-(2-(1,3-dioxoisoindolin-2-yl)ethoxy)-3-oxobutanoate

Product 1

HCID 11157139Amlodipine 2-Phthalimide

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
15 °C

Procedure

116.7 g of ethyl 2-(o-chlorobenzylidene)-4-(2-phthalimidoethoxy)acetoacetate was dissolved in 120 ml of 2-propanol at 80° C. 31.2 g of ethyl-3-aminocrotonate was added and the mixture was heated at the same temperature for 16 hours. The mixture was evaporated to dryness. The residue was dissolved in 180 ml of glacial acetic acid at 80° C. The mixture was cooled to 15° C. and stirred at the same temperature for 20 hours. The solid was filtered off and washed with 92 ml of glacial acetic acid. The solid was dissolved in 75 ml of ethanol at 80° C. The solution was cooled to 20° C. and the suspension was agitated for 2 h. The solid was filtered off, washed with 25 ml of ethanol. The wet product was recrystallized from 60 ml of ethyl acetate.

Workup

  1. temperaturethe mixture was heated at the same temperature for 16 hours
  2. customThe mixture was evaporated to dryness
  3. dissolutionThe residue was dissolved in 180 ml of glacial acetic acid at 80° C
  4. filtrationThe solid was filtered off
  5. washwashed with 92 ml of glacial acetic acid
  6. dissolutionThe solid was dissolved in 75 ml of ethanol at 80° C
  7. temperatureThe solution was cooled to 20° C.
  8. stirringthe suspension was agitated for 2 h
  9. filtrationThe solid was filtered off
  10. washwashed with 25 ml of ethanol
  11. customThe wet product was recrystallized from 60 ml of ethyl acetate

Sources & evidence

ORD record
ord-11271014a8f141d8b8e2c8b197b29cb7
Source dataset
uspto-grants-2005_02
Patent number
US06858738B2

Linked notes

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