2-Butenoic acid, 3-amino-, ethyl ester, (2Z)- → 3-Methyl 5-ethyl 4-(2-chlorophenyl)-2-{[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethoxy]methyl}-6-methyl-1,4-dihydro-3,5-pyridine dicarboxylate

HRID 481033Notes

Reaction equation

HRID 481033 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].[CH2:31]([O:33][C:34](=[O:39])/[CH:35]=[C:36](\[NH2:38])/[CH3:37])[CH3:32]>CC(O)C>[Cl:1][C:2]1[CH:30]=[CH:29][CH:28]=[CH:27][C:3]=1[CH:4]1[C:35]([C:34]([O:33][CH2:31][CH3:32])=[O:39])=[C:36]([CH3:37])[NH:38][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 6437562-Butenoic acid, 3-amino-, ethyl ester, (2Z)-HCID 69267975Methyl 2-(o-chlorobenzylidene)-4-(2-phthalimidoethoxy)acetoacetate

Product 1

HCID 117860093-Methyl 5-ethyl 4-(2-chlorophenyl)-2-{[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethoxy]methyl}-6-methyl-1,4-dihydro-3,5-pyridine dicarboxylate

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
15 °C

Procedure

87 g of methyl 2-(o-chlorobenzylidene)-4-(2-phthalimidoethoxy)acetoacetate was dissolved in 102 ml of 2-propanol at 80° C. 33.1 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 153 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 78 ml of glacial acetic acid. The solid was suspended in 150 ml of methanol and agitated at 60° C. for 30 minutes. The solid was cooled to 20° C. and filtered off, washed with 30 ml of methanol and dried. The product was recrystallized from 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 153 ml of glacial acetic acid at 80° C
  4. filtrationThe solid was filtered off
  5. washwashed with 78 ml of glacial acetic acid
  6. stirringagitated at 60° C. for 30 minutes
  7. temperatureThe solid was cooled to 20° C.
  8. filtrationfiltered off
  9. washwashed with 30 ml of methanol
  10. customdried
  11. customThe product was recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-fe82d828c90e44bc93172871ae6e58f7
Source dataset
uspto-grants-2003_11
Patent number
US06653481B2

Reaction notes

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