Iodine → HCID 22613825, compound

HRID 844549Notes

Reaction equation

HRID 844549 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6](Br)[CH:5]=[C:4]([CH3:9])[CH:3]=1.[Mg].II.[CH2:13]([N:20]1[CH2:25][CH2:24][C:23](=[C:26]([C:32]#[N:33])[C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH2:22][CH2:21]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[Cl-].[NH4+]>C(OCC)C.O1CCCC1>[C:32]([CH:26]([C:23]1([C:6]2[CH:5]=[C:4]([CH3:9])[CH:3]=[C:2]([CH3:1])[CH:7]=2)[CH2:22][CH2:21][N:20]([CH2:13][C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:25][CH2:24]1)[C:27]([O:29][CH2:30][CH3:31])=[O:28])#[N:33]

Participants

8

Reactant 5

HCID 807IodineHCID 25517Ammonium ChlorideHCID 136357Benzene, 1-bromo-3,5-dimethyl-HCID 424752Ethyl 2-(1-benzylpiperidin-4-ylidene)-2-cyanoacetateHCID 5462224Magnesium

Product 1

HCID 22613825HCID 22613825, compoundYield 42.8%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

1,3-Dimethyl-5-bromobenzene (15.6 g) was dissolved in anhydrous diethyl ether (60 ml) and added to a vigorously stirred mixture of magnesium turnings (2.2 g) and 2-3 iodine crystals under a nitrogen atmosphere. Gentle heating was applied to initiate formation of the Grignard reagent and once the spontaneous refluxing had subsided the mixture was heated under reflux for a further 30 minutes. The mixture was cooled in an ice-bath and a solution of ethyl 2-(1-benzylpiperidin-4-ylidene)-2-cyanoacetate (8.0 g) (see Preparation 2) in anhydrous tetrahydrofuran (80 ml) added over 20 minutes. The mixture was stirred at 0° C. for 15 minutes before being left to stand at room temperature for 3 days. The mixture was then poured into saturated aqueous ammonium chloride solution (300 ml) and extracted twice with diethyl ether. The organic extracts were combined and the solvent removed under reduced pressure to give a residue which was chromatographed on silca gel eluting with a solvent gradient of 3:0 changing to 3:1, by volume, dichloromethane:diethyl ether to give the title compound (4.7 g) as an oil.

Workup

  1. temperatureGentle heating
  2. temperatureonce the spontaneous refluxing
  3. temperaturewas heated
  4. temperatureunder reflux for a further 30 minutes
  5. temperatureThe mixture was cooled in an ice-bath
  6. waitbefore being left
  7. waitto stand at room temperature for 3 days
  8. extractionextracted twice with diethyl ether
  9. customthe solvent removed under reduced pressure
  10. customto give a residue which
  11. customwas chromatographed on silca gel
  12. washeluting with a solvent gradient of 3:0 changing to 3:1, by volume, dichloromethane

Sources & evidence

ORD record
ord-984d0f49ed5b469ba473706163420b94
Source dataset
uspto-grants-2002_04
Patent number
US06380396B1

Reaction notes

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