Sodium Hydroxide → Dimethyl 4-(2,6-dichlorophenyl)-2-(4-methyl-1-piperazinyl)carbonylmethyl-6-(2-phenylethyl)-1,4-dihydropyridine-3,5-dicarboxylate

HRID 342499Notes

Reaction equation

HRID 342499 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[CH:9]1[C:14]([C:15]([O:17][CH3:18])=[O:16])=[C:13]([CH2:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[NH:12][C:11]([CH2:27][C:28](OC)=[O:29])=[C:10]1[C:32]([O:34][CH3:35])=[O:33].[OH-].[Na+].[CH3:38][N:39]1[CH2:44][CH2:43][NH:42][CH2:41][CH2:40]1.Cl.C(N=C=NCCCN(C)C)C>ClCCl.CCOCC.O.CO>[Cl:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=1[CH:9]1[C:14]([C:15]([O:17][CH3:18])=[O:16])=[C:13]([CH2:19][CH2:20][C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[NH:12][C:11]([CH2:27][C:28]([N:42]2[CH2:43][CH2:44][N:39]([CH3:38])[CH2:40][CH2:41]2)=[O:29])=[C:10]1[C:32]([O:34][CH3:35])=[O:33]

Participants

9

Reactant 4

HCID 14798Sodium HydroxideHCID 531671-MethylpiperazineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 70203360Dimethyl 4-(2,6-dichlorophenyl)-2-methoxycarbonylmethyl-6-(2-phenylethyl)-1,4-dihydropyridine-3,5-dicarboxylate

Product 1

HCID 86753550Dimethyl 4-(2,6-dichlorophenyl)-2-(4-methyl-1-piperazinyl)carbonylmethyl-6-(2-phenylethyl)-1,4-dihydropyridine-3,5-dicarboxylateYield 59.6%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of dimethyl 4-(2,6-dichlorophenyl)-2-methoxycarbonylmethyl-6-(2-phenylethyl)-1,4-dihydropyridine-3,5-dicarboxylate (3.9 g, 7.52 mmol), methanol(35 ml), water (5 ml), and 6N NaOH (2.51 ml, 15.05 mmol) was stirred at room temperature for 1.25 h. The reaction mixture was diluted with dichloromethane (100 ml) followed by addition of 6 NHCl (3 ml) and water (100 ml). The organic layer separated was washed twice with water and brine, dried over Na2SO4, and concentrated to 50 ml. To this solution was added N-methylpiperazine (1.25 ml, 11.28 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (2.162 g, 11.28 mmol) at 0° C. and stirred for 0.5 h, then ice bath was removed and stirring was continued at room temperature overnight. The reaction mixture was washed with water, NaHCO3 aqueous solution and brine, and dried over Na2SO4. The solvent was evaporated and the crude product was chromatographed on 234 g silica gel (dichloromethane/ethyl acetate: 22/3 as eluent) to give 3.48 g. This was taken up in 17 ml ether and stirred, giving 2.63 g of crystals after drying under high vacuum at 78° C., mp 138°-139° C.

Workup

  1. customThe organic layer separated
  2. washwas washed twice with water and brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated to 50 ml
  5. stirringstirred for 0.5 h
  6. customice bath was removed
  7. stirringstirring
  8. waitwas continued at room temperature overnight
  9. washThe reaction mixture was washed with water, NaHCO3 aqueous solution and brine
  10. dry with materialdried over Na2SO4
  11. customThe solvent was evaporated
  12. customthe crude product was chromatographed on 234 g silica gel (dichloromethane/ethyl acetate: 22/3 as eluent)
  13. customto give 3.48 g
  14. stirringstirred

Sources & evidence

ORD record
ord-b97f31b8d700420498bc90de94c8fcf0
Source dataset
uspto-grants-1999_01
Patent number
US05859011

Reaction notes

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