Methyl acetoacetate → Nifedipine

HRID 893796Notes

Reaction equation

HRID 893796 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 77.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Into an enamelled 250 liter autoclave 25 kg (0.165 kmole) of 2-nitro-benzaldehyde, 53 kg (0.456 kmole) of methyl acetoacetate, 16 kg (0.235 kmole) of a 25% aqueous ammonium hydroxide solution and 80 liter of methanol are weighed in. The apparatus is closed and the reaction mixture is stirred at a temperature of 101°-103° C. and a pressure of 2.0-2.2 bar for 5 hours. The reaction mixture is then cooled to 0°-5° C., the precipitated nifedipine is filtered and washed with methanol. Thus 44.4 kg of nifedipine are obtained, yield 77.5%. According to TLC the product is uniform. According to HPLC the nifedipine content amounts to 98.24%. The product complies with the requirements of USP XXI without further purification. M. p.: 171.5°-175° C.

Workup

  1. customThe apparatus is closed
  2. temperatureThe reaction mixture is then cooled to 0°-5° C.
  3. filtrationthe precipitated nifedipine is filtered
  4. washwashed with methanol

Sources & evidence

ORD record
ord-f13029afa58442baa8145d72472938a0
Source dataset
uspto-grants-1992_06
Patent number
US05126457

Reaction notes

Loading…