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Nifedipine → N-Methylnifedipine

HRID 399373
Notes
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Reaction equation

HRID 399373 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]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 4485NifedipineHCID 6328Methyl iodideHCID 8857Ethyl AcetateHCID 24758Sodium hydride2×

Product 1

HCID 14817573N-Methylnifedipine

Reagents, catalysts & solvents 3

HCID 7909Methyl Isobutyl KetoneSolvent
HCID 8028TetrahydrofuranSolvent
HCID 8058HexaneSolvent

Conditions

Temperature
38 °C

Procedure

12 g of nifedipine was disclosed in 50 ml of tetrahydrofuran in a nitrogen atmosphere. 1.66 g of a sodium hydride/oil dispersion (60% NaH) was added under agitation. Following agitation for some time, 10 ml of methyl iodide was added, and the resulting mixture was agitated for 1 hour at 38° 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. The solid obtained was dissolved in 200 ml of MIBK, and hexane was added producing 8.9 g of N-methylnifedipine in the form of yellow crystals. This compound had a melting point of 184° to 187° C.; an infrared absorption spectrum of 1690 cm-1 ; C=O, 1524 cm-1 ; N--O), and a proton-NMR spectrum (solvent: CDCl3) of 2.5 (6 H, 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

  1. additionwas added
  2. washThe resulting organic layer was washed several times with water
  3. filtrationThe sodium sulfate was filtered out
  4. customthe solvent was removed
  5. customThe solid obtained

Sources & evidence

ORD record
ord-df6e601094554948acb93bc45d40cf8c
Source dataset
uspto-grants-1998_10
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US05820944

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes