Sodium Iodide → (E)-1-[1-(3,4-difluorobenzyl)-(3S)-pyrrolidin-3-yl]-3-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene]piperidin-2-one

HRID 1362660Notes

Reaction equation

HRID 1362660 reaction equation
C(O[C:4](=[O:25])/[C:5](=[CH:10]/[C:11]1[CH:16]=[CH:15][C:14]([N:17]2[CH:21]=[C:20]([CH3:22])[N:19]=[CH:18]2)=[C:13]([O:23][CH3:24])[CH:12]=1)/[CH2:6][CH2:7][CH2:8]Cl)C.Cl.Cl.[F:28][C:29]1[CH:30]=[C:31]([CH:39]=[CH:40][C:41]=1[F:42])[CH2:32][N:33]1[CH2:37][CH2:36][C@H:35]([NH2:38])[CH2:34]1.C(=O)([O-])[O-].[K+].[K+].[I-].[Na+]>C(#N)C.O>[F:28][C:29]1[CH:30]=[C:31]([CH:39]=[CH:40][C:41]=1[F:42])[CH2:32][N:33]1[CH2:37][CH2:36][C@H:35]([N:38]2[CH2:8][CH2:7][CH2:6]/[C:5](=[CH:10]\[C:11]3[CH:16]=[CH:15][C:14]([N:17]4[CH:21]=[C:20]([CH3:22])[N:19]=[CH:18]4)=[C:13]([O:23][CH3:24])[CH:12]=3)/[C:4]2=[O:25])[CH2:34]1

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 66960126HCID 66960126, compoundHCID 66960173((3S)-1-(3,4-difluorobenzyl)pyrrolidine-3-yl)amine dihydrochloride

Product 1

HCID 59170975(E)-1-[1-(3,4-difluorobenzyl)-(3S)-pyrrolidin-3-yl]-3-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene]piperidin-2-oneYield 73.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To a solution of (E)-5-chloro-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valeric acid ethyl ester (200 mg) and ((3S)-1-(3,4-difluorobenzyl)pyrrolidine-3-yl)amine dihydrochloride (315 mg) in acetonitrile (8 mL) and water (2 mL), potassium carbonate (228 mg) and sodium iodide (831 mg) were added. After carrying out heat-refluxing of the reaction solution for 12 hours, the reaction solution allowed to be cooled to room temperature and concentrated under reduced pressure. A 2N sodium hydroxide solution (1 mL) in ethanol (5 mL) was added to the obtained residue. After agitating the reaction mixture at room temperature for 12 hours, it was neutralized with a 5N hydrochloric acid solution, and the reaction solution was extracted with ethyl acetate. After the obtained organic layer was washed with a saturated saline solution, it was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. 200 mg of the title compound was obtained by purifying the residue by silica gel chromatography (Carrier: Chromatorex™ NH; elution solvent: ethyl acetate). The physical properties of the compound are as follows.

Workup

  1. temperatureAfter carrying out heat-refluxing of the reaction solution for 12 hours
  2. concentrationconcentrated under reduced pressure
  3. additionA 2N sodium hydroxide solution (1 mL) in ethanol (5 mL) was added to the obtained residue
  4. extractionthe reaction solution was extracted with ethyl acetate
  5. washAfter the obtained organic layer was washed with a saturated saline solution, it
  6. dry with materialwas dried over anhydrous magnesium sulfate
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-bc524213ac074a699432f91b3b0011de
Source dataset
uspto-grants-2011_02
Patent number
US07880009B2

Reaction notes

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