Chloroform → Nicardipine Hydrochloride

HRID 622175

Reaction equation

HRID 622175 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:10]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([N+:17]([O-:19])=[O:18])[CH:12]=2)[C:9]([C:20]([OH:22])=[O:21])=[C:8]([CH3:23])[NH:7][C:6]=1[CH3:24])=[O:4].O[CH2:26][CH2:27][N:28]([CH3:36])[CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C1(N=C=NC2CCCCC2)CCCCC1.C(Cl)(Cl)[Cl:53]>>[ClH:53].[CH3:23][C:8]1[NH:7][C:6]([CH3:24])=[C:5]([C:3]([O:2][CH3:1])=[O:4])[CH:10]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([N+:17]([O-:19])=[O:18])[CH:12]=2)[C:9]=1[C:20]([O:22][CH2:26][CH2:27][N:28]([CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH3:36])=[O:21]

Participants

5

Reactant 4

HCID 6212ChloroformHCID 10868DicyclohexylcarbodiimideHCID 66876N-Benzyl-N-methylethanolamineHCID 1733222,6-Dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid monomethyl ester

Product 1

HCID 41114Nicardipine HydrochlorideYield 85.4%

Procedure

A mixture of 3-methoxycarbonyl-2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-5-carboxylic acid (3.32 g, 0.01 mole), N-(2-hydroxyethyl)-N-benzyl-methylamine (4.98 g) and N,N'-dicyclohexylcarbodiimide (DCC) (2.05 g) is stirred at 60°-80° C. for 1 hour. To the reaction mixture chloroform (16 ml) is added and the mixture is washed with water (3×50 ml). Then the organic layer is washed with a 10% aqueous solution of HCl (16 ml) and water (3×10 ml). The organic layer is dried with anhydrous Na2SO4 and the solvent is evaporated in vacuo. The oily residue is dissolved in ethyl acetate (18 ml) and stirred at 0° C. for 2 hours. The precipitate, which separates, is filtered off, dried in vacuo and recrystallized from acetone. Thus, there is obtained the title compound nicardipine hydrochloride (4.4 g, 85.4%).

Workup

  1. washthe mixture is washed with water (3×50 ml)
  2. washThen the organic layer is washed with a 10% aqueous solution of HCl (16 ml) and water (3×10 ml)
  3. dry with materialThe organic layer is dried with anhydrous Na2SO4
  4. customthe solvent is evaporated in vacuo
  5. dissolutionThe oily residue is dissolved in ethyl acetate (18 ml)
  6. stirringstirred at 0° C. for 2 hours
  7. filtrationis filtered off
  8. customdried in vacuo
  9. customrecrystallized from acetone

Sources & evidence

ORD record
ord-7b6da278485948ff8040dbb04421b14c
Source dataset
uspto-grants-1988_09
Patent number
US04769465

Linked notes

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