Methyl acetoacetate → Nifedipine

HRID 893793Notes

Reaction equation

HRID 893793 reaction equation
[N+:1]([C:4]1[CH:11]=[CH:10][CH:9]=[CH:8][C:5]=1[CH:6]=O)([O-:3])=[O:2].[C:12]([O:18][CH3:19])(=[O:17])[CH2:13][C:14]([CH3:16])=O.[OH-:20].[NH4+:21]>CO>[CH3:16][C:14]1[NH:21][C:14]([CH3:16])=[C:13]([C:12]([O:18][CH3:19])=[O:17])[CH:6]([C:5]2[CH:8]=[CH:9][CH:10]=[CH:11][C:4]=2[N+:1]([O-:3])=[O:2])[C:13]=1[C:12]([O:18][CH3:19])=[O:20]

Participants

5

Reactant 3

HCID 7757Methyl acetoacetateHCID 111012-NitrobenzaldehydeHCID 14923Ammonium Hydroxide

Product 1

HCID 4485NifedipineYield 79.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Into a 1-liter glass reactor 60.4 g (0.4 mole) of 2-nitro-benzaldehyde, 102.1 g (0.88 mole) of methyl acetoacetate, 28.25 g (0.415 mole) of a 25% aqueous ammonium hydroxide solution and 150 ml of methanol are weighed in. The reactor is closed, whereupon the reaction mixture is heated to boiling at a temperature of 101°-103° C. and a pressure of 2.0-2.2 bar for 5 hours. The reaction mixture is cooled to 0°-5° C., the precipitated product is filtered and washed with methanol. Thus 110.5 g of nifedipine are obtained, yield 79.8%, m.p.: 171.5°-175° C.

Workup

  1. customThe reactor is closed, whereupon the reaction mixture
  2. temperatureis heated
  3. customto boiling at a temperature of 101°-103° C.
  4. temperatureThe reaction mixture is cooled to 0°-5° C.
  5. filtrationthe precipitated product is filtered
  6. washwashed with methanol

Sources & evidence

ORD record
ord-a54e33fcbc474bd8bedc07291d8e6751
Source dataset
uspto-grants-1992_06
Patent number
US05126457

Reaction notes

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