Potassium Carbonate → Niguldipine hydrochloride, (+/-)-

HRID 981998Notes

Reaction equation

HRID 981998 reaction equation
[CH3:1][C:2]1[NH:3][C:4]([CH3:28])=[C:5]([C:21]([O:23][CH2:24][CH2:25][CH2:26]Br)=[O:22])[CH:6]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([N+:18]([O-:20])=[O:19])[CH:13]=2)[C:7]=1[C:8]([O:10][CH3:11])=[O:9].[ClH:29].[C:30]1([C:36]2([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]2)[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.O>[ClH:29].[CH3:1][C:2]1[NH:3][C:4]([CH3:28])=[C:5]([C:21]([O:23][CH2:24][CH2:25][CH2:26][N:39]2[CH2:40][CH2:41][C:36]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)[CH2:37][CH2:38]2)=[O:22])[CH:6]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([N+:18]([O-:20])=[O:19])[CH:13]=2)[C:7]=1[C:8]([O:10][CH3:11])=[O:9]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 30475044,4-Diphenylpiperidine hydrochlorideHCID 32742783-bromopropyl Methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate

Product 1

HCID 357904Niguldipine hydrochloride, (+/-)-Yield 86.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A mixture of 13 g of 3-methyl 5-(3-bromopropyl) (+)-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-pyridine-3,5-dicarboxylate, 7.85 g of 4,4-diphenylpiperidine hydrochloride and 12 g of potassium carbonate in 120 ml of toluene and 25 ml of water is refluxed for 14 h under a nitrogen atmosphere and with vigorous stirring. After cooling, the phases are separated; the organic phase is washed twice with water, dried over sodium sulphate and evaporated in vacuo. The oily residue is dissolved in 140 ml of dioxane, after which 2.3 ml of concentrated hydrochloric acid solution (12.5 M, d=1.19) are added and 20-25 ml of the solvent mixture are then distilled off in vacuo. On standing at room temperature, the product crystallises spontaneously or after trituration and is filtered off under suction after 16 h, washed with dioxane and diisopropyl ether and dried in vacuo at 80° C. 16 g of the title compound of m.p. 158°-160° C. and [α]22D =+14.4° (c=1, methanol) are obtained.

Workup

  1. temperatureis refluxed for 14 h under a nitrogen atmosphere and with vigorous stirring
  2. temperatureAfter cooling
  3. customthe phases are separated
  4. washthe organic phase is washed twice with water
  5. dry with materialdried over sodium sulphate
  6. customevaporated in vacuo
  7. dissolutionThe oily residue is dissolved in 140 ml of dioxane
  8. additionafter which 2.3 ml of concentrated hydrochloric acid solution (12.5 M, d=1.19) are added
  9. distillation20-25 ml of the solvent mixture are then distilled off in vacuo
  10. customOn standing at room temperature
  11. customthe product crystallises spontaneously
  12. filtrationafter trituration and is filtered off under suction after 16 h
  13. washwashed with dioxane and diisopropyl ether
  14. customdried in vacuo at 80° C

Sources & evidence

ORD record
ord-c7e5bdd2dc594fa7996ff4f4bcbd5534
Source dataset
uspto-grants-1991_02
Patent number
US04994461

Reaction notes

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