Methyl acetoacetate → Nifedipine

Participants

Reaction Steps

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.

Provenance & Evidence