Potassium Iodide → 2-(4-Methoxyphenyl)-N-(4-methylbenzyl)-N-[1-(2-methylthiazol-4-ylmethyl)piperidin-4-yl]acetamide

HRID 929735Notes

Reaction equation

HRID 929735 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([N:12]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][CH:21]=2)[CH:13]2[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)=[O:11])=[CH:5][CH:4]=1.Cl.Cl[CH2:29][C:30]1[N:31]=[C:32]([CH3:35])[S:33][CH:34]=1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>C(#N)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:9][C:10]([N:12]([CH2:19][C:20]2[CH:21]=[CH:22][C:23]([CH3:26])=[CH:24][CH:25]=2)[CH:13]2[CH2:14][CH2:15][N:16]([CH2:29][C:30]3[N:31]=[C:32]([CH3:35])[S:33][CH:34]=3)[CH2:17][CH2:18]2)=[O:11])=[CH:7][CH:8]=1

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 27342034-(Chloromethyl)-2-methyl-1,3-thiazole--hydrogen chloride (1/1)HCID 99465262-(4-Methoxyphenyl)-N-(4-methylbenzyl)-N-(piperidin-4-yl)acetamide

Product 1

HCID 689526972-(4-Methoxyphenyl)-N-(4-methylbenzyl)-N-[1-(2-methylthiazol-4-ylmethyl)piperidin-4-yl]acetamide

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
82 °C

Procedure

50ELH87 (0.3 g, 0.852 mmol, 1.0 eq) and 4-(chloromethyl)-2-methylthiazole hydrochloride (0.235 g, 1.5 eq) were added to a 7 ml vial and dissolved in acetonitrile (3 ml). Potassium carbonate (141.3 g, 1.2 eq) and a crystal of potassium iodide were added and the vial was sealed and shaken for 20 h at 82° C. The reaction mixture was extracted with distilled water (made basic by potassium carbonate, pH 10) and dichloromethane. The crude product was dried with sodium sulfate and concentrated. After purification by HPLC the product was converted into the hydrochloride salt by dissolving the free base in 1 ml dichloromethane and adding 1 eq. HCl in ether (2M). This mixture was added drop-wise to an excess of heptane where the product precipitated. The solvent was removed by evaporation leaving a white powder as the product. yield 83.8 mg (21%), UV/MS 100/90 (M+ 463), rt (B, MS) 11.82.

Workup

  1. customthe vial was sealed
  2. extractionThe reaction mixture was extracted with distilled water (made basic by potassium carbonate, pH 10) and dichloromethane
  3. dry with materialThe crude product was dried with sodium sulfate
  4. concentrationconcentrated
  5. customAfter purification by HPLC the product
  6. dissolutionby dissolving the free base in 1 ml dichloromethane
  7. additionadding 1 eq
  8. additionThis mixture was added drop-wise to an excess of heptane where the product
  9. customprecipitated
  10. customThe solvent was removed by evaporation
  11. customleaving a white powder as the product
  12. customyield 83.8 mg (21%), UV/MS 100/90 (M+ 463), rt (B, MS) 11.82

Sources & evidence

ORD record
ord-9059f99f9ad349e98a4bfbba22d68c5b
Source dataset
uspto-grants-2016_03
Patent number
US09296694B2

Reaction notes

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