Isopropanol → Watanidipine

HRID 260680Notes

Reaction equation

HRID 260680 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][CH:11]=1)[CH:7]=O)([O-:3])=[O:2].[C:12]([O:18][CH2:19][CH2:20][C:21]1[CH:26]=[CH:25][C:24]([N:27]2[CH2:32][CH2:31][N:30]([CH:33]([C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[CH2:29][CH2:28]2)=[CH:23][CH:22]=1)(=[O:17])[CH2:13]C(C)=O.[NH2:46]/[C:47](/[CH3:53])=[CH:48]\[C:49]([O:51][CH3:52])=[O:50].[CH:54](O)(C)[CH3:55]>>[CH3:54][C:55]1[NH:46][C:47]([CH3:53])=[C:48]([C:49]([O:51][CH3:52])=[O:50])[CH:7]([C:6]2[CH:9]=[CH:10][CH:11]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=2)[C:13]=1[C:12]([O:18][CH2:19][CH2:20][C:21]1[CH:26]=[CH:25][C:24]([N:27]2[CH2:32][CH2:31][N:30]([CH:33]([C:34]3[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=3)[C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[CH2:29][CH2:28]2)=[CH:23][CH:22]=1)=[O:17]

Participants

5

Reactant 4

HCID 3776IsopropanolHCID 74493-NitrobenzaldehydeHCID 643918Methyl 3-aminocrotonateHCID 14903417HCID 14903417, compound

Product 1

HCID 122073WatanidipineYield 48%

Procedure

3-Nitrobenzaldehyde (1.144 g, 7.57 mmol), [p-(4-benzhydrylpiperazino)phenyl]ethyl acetoacetate (3.464 g, 7.59 mmol) and methyl 3-aminocrotonate (873 mg, 7.58 mmol) were charged in a 100 ml-eggplant type flask. Isopropanol (12 ml) was added thereto. The flask was equipped with a Dimroth condenser and refluxed under heating for 16 hours. The reaction solvent was distilled away under reduced pressure and the residue was separated by column chromatography [silica gel, chloroform--methanol (45:1)] and column chromatography [silica gel, ethyl acetate--n-hexane (2:3)], and the crude product obtained was purified by high performance liquid chromatography to give 2.503 g of the title Compound 1 (yield 48%).

Workup

  1. customThe flask was equipped with a Dimroth condenser
  2. temperaturerefluxed
  3. temperatureunder heating for 16 hours
  4. distillationThe reaction solvent was distilled away under reduced pressure
  5. customthe residue was separated by column chromatography [silica gel, chloroform--methanol (45:1)] and column chromatography [silica gel, ethyl acetate--n-hexane (2:3)]
  6. customthe crude product obtained
  7. customwas purified by high performance liquid chromatography

Sources & evidence

ORD record
ord-a9cbb276d5664ec18ab532622c7cf945
Source dataset
uspto-grants-1996_06
Patent number
US05530001

Reaction notes

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