Potassium Iodide → 4-[4-(6-Methylthieno[2,3-d]isoxazol-3-yl)-piperidin-1-yl]-butyronitrile

HRID 1986916Notes

Reaction equation

HRID 1986916 reaction equation
C(=O)([O-])[O-].[K+].[K+].[I-].[K+].Br[CH2:10][CH2:11][CH2:12][C:13]#[N:14].Cl.[CH3:16][C:17]1[C:24]2[O:23][N:22]=[C:21]([CH:25]3[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]3)[C:20]=2[S:19][CH:18]=1>C(#N)C.O>[CH3:16][C:17]1[C:24]2[O:23][N:22]=[C:21]([CH:25]3[CH2:30][CH2:29][N:28]([CH2:10][CH2:11][CH2:12][C:13]#[N:14])[CH2:27][CH2:26]3)[C:20]=2[S:19][CH:18]=1

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 214124-BromobutyronitrileHCID 231124496-methyl-3-piperidin-4-yl-thieno[2,3-d]isoxazole Hydrochloride

Product 1

HCID 231368314-[4-(6-Methylthieno[2,3-d]isoxazol-3-yl)-piperidin-1-yl]-butyronitrileYield 31%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

Add potassium carbonate (17.72 mmol, 2.45 g, 2.40 equivalents), potassium iodide (0.73 mmol, 123 mg, 0.10 equivalents), and 4-bromobutyronitrile (8.86 mmol, 0.88 mL, 1.20 equivalents) to a stirred solution of 6-methyl-3-piperidin-4-yl-thieno[2,3-d]isoxazole hydrochloride (7.38 mmol, 1.91 g, 1.00 equivalents) in acetonitrile (10.84 mL) and water (3.60 mL). Stir the resulting mixture at reflux overnight. Cool to room temperature, filter the reaction mixture and wash the solid material collected with dichloromethane and evaporate the filtrate. Take the residue up in dichloromethane (45 mL), wash with sodium hydroxide (aqueous, 18 mL, 2 M), water (18 mL), saturated sodium hydroxide (aqueous, 18 mL), dry over magnesium sulfate, filter and evaporate. Purify the residue via flash column chromatography using a gradient and eluting with a mixture of n-heptane : ethyl acetate (0.5:9.5) to ethyl acetate (100%) to yield the desired product as a brown oil (663 mg). LC/MS (ESI), m/e 290 (MH+), retention time 1.19 minutes. Condition II.

Workup

  1. temperatureat reflux overnight
  2. filtrationfilter the reaction mixture
  3. washwash the solid material
  4. customcollected with dichloromethane
  5. customevaporate the filtrate
  6. washwash with sodium hydroxide (aqueous, 18 mL, 2 M), water (18 mL), saturated sodium hydroxide (aqueous, 18 mL)
  7. dry with materialdry over magnesium sulfate
  8. filtrationfilter
  9. customevaporate
  10. customPurify the residue via flash column chromatography
  11. washeluting with a mixture of n-heptane : ethyl acetate (0.5:9.5) to ethyl acetate (100%)

Sources & evidence

ORD record
ord-36c38470711b4871a04696d076547346
Source dataset
uspto-grants-2009_06
Patent number
US07550469B2

Reaction notes

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