2-Chlorobenzaldehyde → Phthalimidoamlodipine

HRID 652077Notes

Reaction equation

HRID 652077 reaction equation
[NH2:1]/[C:2](/[CH3:8])=[CH:3]\[C:4]([O:6][CH3:7])=[O:5].[Cl:9][C:10]1[CH:17]=[CH:16][CH:15]=[CH:14][C:11]=1[CH:12]=O.[C:18]1(=[O:40])[N:22]([CH2:23][CH2:24][O:25][CH2:26][C:27](=O)[CH2:28][C:29]([O:31][CH2:32][CH3:33])=[O:30])[C:21](=[O:35])[C:20]2=[CH:36][CH:37]=[CH:38][CH:39]=[C:19]12>C(O)(C)C>[Cl:9][C:10]1[CH:17]=[CH:16][CH:15]=[CH:14][C:11]=1[CH:12]1[C:3]([C:4]([O:6][CH3:7])=[O:5])=[C:2]([CH3:8])[NH:1][C:27]([CH2:26][O:25][CH2:24][CH2:23][N:22]2[C:21](=[O:35])[C:20]3=[CH:36][CH:37]=[CH:38][CH:39]=[C:19]3[C:18]2=[O:40])=[C:28]1[C:29]([O:31][CH2:32][CH3:33])=[O:30]

Participants

5

Reactant 3

HCID 69962-ChlorobenzaldehydeHCID 643918Methyl 3-aminocrotonateHCID 9840027Ethyl 4-(2-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)ethoxy)-3-oxobutanoate

Product 1

HCID 9871958Phthalimidoamlodipine

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

Methyl 3-aminocrotonate (72.2 g; 0.627M) and 2-chlorobenzaldehyde (88.1 g; 0.627M) were added to a solution of ethyl 4-(2-phthalimidoethoxy)acetoacetate (200 g; 0.627M) in isopropanol (1 liter) and the mixture was heated under reflux for 20 hours. The isopropanol was evaporated under reduced pressure and replaced by acetic acid (1 liter). After granulation at 10° the solid was collected and slurried in methanol (300 ml). The solid was collected by filtration and dried in vacuo at 50° to afford the title compound, yield 84.4 g, m.p. 146°-147°.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 20 hours
  3. customThe isopropanol was evaporated under reduced pressure
  4. customAfter granulation at 10° the solid was collected
  5. filtrationThe solid was collected by filtration
  6. customdried in vacuo at 50°

Sources & evidence

ORD record
ord-a4ce0027ed954f5eafb3d35b6c7d99f5
Source dataset
uspto-grants-1987_06
Patent number
US04670449

Reaction notes

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