Methyl 3-aminocrotonate → Palonidipine

HRID 483203Notes

Reaction equation

HRID 483203 reaction equation
[C:1]([O:7][CH2:8][C:9]([CH2:22]C)([CH2:20]C)[CH2:10][N:11]([CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH3:12])(=[O:6])[CH2:2][C:3]([CH3:5])=O.[NH2:24]/[C:25](/[CH3:31])=[CH:26]\[C:27]([O:29][CH3:30])=[O:28].[F:32][C:33]1[CH:40]=[CH:39][C:38]([N+:41]([O-:43])=[O:42])=[CH:37][C:34]=1[CH:35]=O>CC(O)C>[CH3:5][C:3]1[NH:24][C:25]([CH3:31])=[C:26]([C:27]([O:29][CH3:30])=[O:28])[CH:35]([C:34]2[CH:37]=[C:38]([N+:41]([O-:43])=[O:42])[CH:39]=[CH:40][C:33]=2[F:32])[C:2]=1[C:1]([O:7][CH2:8][C:9]([CH3:20])([CH3:22])[CH2:10][N:11]([CH2:13][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)[CH3:12])=[O:6]

Participants

5

Reactant 3

HCID 643918Methyl 3-aminocrotonateHCID 27347702-Fluoro-5-nitrobenzaldehydeHCID 538443023-(N-benzyl-N-methylamino)-2,2-diethylpropyl acetoacetate

Product 1

HCID 119154PalonidipineYield 261.7%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

To a solution of a mixture 290 mg of 3-(N-benzyl-N-methylamino)-2,2-diethylpropyl acetoacetate and 15 mg of methyl 3-aminocrotonate in 1 ml of 2-propanol was added 168 mg of 2-fluoro-5-nitrobenzaldehyde. The mixture was refluxed for 10 hours. The solvent was distilled off to leave the residue. The residue was purified by a column chromatography (n-hexane:ethyl acetate=2:1) on silica gel to provide 184 mg (yield 34%) of the desirec compound (140).

Workup

  1. temperatureThe mixture was refluxed for 10 hours
  2. distillationThe solvent was distilled off
  3. customto leave the residue
  4. customThe residue was purified by a column chromatography (n-hexane:ethyl acetate=2:1) on silica gel

Sources & evidence

ORD record
ord-2004f57b0659404c8b3690d3be96f4e7
Source dataset
uspto-grants-1986_03
Patent number
US04578395

Reaction notes

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