Methyl 3-aminocrotonate → 4-(2-Chlorophenyl)-2-[[2-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)ethoxy]methyl]-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylic Acid 3,5-Dimethyl Ester

HRID 25477

Reaction equation

HRID 25477 reaction equation
[Cl:1][C:2]1[CH:30]=[CH:29][CH:28]=[CH:27][C:3]=1[CH:4]=[C:5]([C:10]([CH2:12][O:13][CH2:14][CH2:15][N:16]1[C:20](=[O:21])[C:19]2=[CH:22][CH:23]=[CH:24][CH:25]=[C:18]2[C:17]1=[O:26])=O)[C:6]([O:8][CH3:9])=[O:7].[CH3:31][O:32][C:33](=[O:38])/[CH:34]=[C:35](\[NH2:37])/[CH3:36]>CC(O)C>[Cl:1][C:2]1[CH:30]=[CH:29][CH:28]=[CH:27][C:3]=1[CH:4]1[C:34]([C:33]([O:32][CH3:31])=[O:38])=[C:35]([CH3:36])[NH:37][C:10]([CH2:12][O:13][CH2:14][CH2:15][N:16]2[C:20](=[O:21])[C:19]3[C:18](=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:17]2=[O:26])=[C:5]1[C:6]([O:8][CH3:9])=[O:7]

Participants

4

Reactant 2

HCID 643918Methyl 3-aminocrotonateHCID 69267975Methyl 2-(o-chlorobenzylidene)-4-(2-phthalimidoethoxy)acetoacetate

Product 1

HCID 112609924-(2-Chlorophenyl)-2-[[2-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)ethoxy]methyl]-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylic Acid 3,5-Dimethyl Ester

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
15 °C

Procedure

92.1 g of methyl 2-(o-chlorobenzylidene)-4-(2-phthalimidoethoxy)acetoacetate was dissolved in 108 ml of 2-propanol at 80° C. 31.3 g of methyl-3-aminocrotonate was added and the mixture was heated at the same temperature for 24 hours. The mixture was evaporated to dryness. The residue was dissolved in 162 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 83 ml of glacial acetic acid. The solid was suspended in 68 ml of methanol and agitated for 30 minutes. The solid was filtered off, washed with 23 ml of methanol and dried. The product was recrystallized from ethyl acetate.

Workup

  1. temperaturethe mixture was heated at the same temperature for 24 hours
  2. customThe mixture was evaporated to dryness
  3. dissolutionThe residue was dissolved in 162 ml of glacial acetic acid at 80° C
  4. filtrationThe solid was filtered off
  5. washwashed with 83 ml of glacial acetic acid
  6. stirringagitated for 30 minutes
  7. filtrationThe solid was filtered off
  8. washwashed with 23 ml of methanol
  9. customdried
  10. customThe product was recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-37af752ca5b5457c9f1e81b7de7d9e72
Source dataset
uspto-grants-2005_02
Patent number
US06858738B2

Linked notes

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