Nifedipine → N-Methylnifedipine

HRID 1870079Notes

Reaction equation

[CH3:1][C:2]1[NH:7][C:6]([CH3:8])=[C:5]([C:9]([O:11][CH3:12])=[O:10])[CH:4]([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:18]=2[N+:19]([O-:21])=[O:20])[C:3]=1[C:22]([O:24][CH3:25])=[O:23].[H-].[Na+].CI.[C:30](OCC)(=O)C>O1CCCC1.CC(CC(C)=O)C.CCCCCC>[CH3:1][C:2]1[N:7]([CH3:30])[C:6]([CH3:8])=[C:5]([C:9]([O:11][CH3:12])=[O:10])[CH:4]([C:13]2[C:18]([N+:19]([O-:21])=[O:20])=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:3]=1[C:22]([O:24][CH3:25])=[O:23]

Participants

Conditions

Temperature: 88 °C

Procedure

12 g of nifedipine was dissolved in 50 ml of tetrahydrofuran under a nitrogen atmosphere. 1.66 g of a sodium hydride/oil dispersion (60% NaH) was added. Following agitation for some time, 10 ml of methyl iodide was added, and the resulting mixture was agitated for 1 hour at 88° C. 200 ml of ethyl acetate was then added. The resulting organic layer was washed several times with water, and was then dehydrated with sodium sulfate. The sodium sulfate was filtered out, and the solvent was removed from the filtrate by means of a rotary evaporator. The solid obtained was dissolved in 200 ml of MIBK, and hexane was added to this, producing 8.9 g of N-methylnifedipine in the form of yellow crystals. This compound had a melting point of 184 to 187° C., infrared absorption spectrum of 1690 cm-1 : C=O, 1524 cm-1 : N--O, and proton-NMR spectrum (solvent: CDCl3): 2.5 (6H, methyl), 3.3 (3H, N-methyl), 3.6 (6H, O-methyl), 5.7 (1H, C--H), 7.2-7.6 (4H, C--H in aromatic nucleus).

Workup

additionwas added
washThe resulting organic layer was washed several times with water
filtrationThe sodium sulfate was filtered out
customthe solvent was removed from the filtrate by means of a rotary evaporator
customThe solid obtained

Sources & evidence

ORD record: ord-7bbca05432fb4e42b1498c04a20d0351
Source dataset: uspto-grants-2000_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06096483

Reaction notes

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