Potassium Carbonate → 4-(4-(4-Fluorophenyl)thiazol-2-yl)-2,2-dimethyltetrahydro-2H-pyran-4-carbonitrile

HRID 1397254Notes

Reaction equation

HRID 1397254 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]([CH2:13][C:14]#[N:15])[S:11][CH:12]=2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].Cl[CH2:23][C:24]([O:27][CH2:28][CH2:29]Cl)([CH3:26])[CH3:25]>CN(C=O)C.C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:9]=[C:10]([C:13]3([C:14]#[N:15])[CH2:29][CH2:28][O:27][C:24]([CH3:26])([CH3:25])[CH2:23]3)[S:11][CH:12]=2)=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 11430Potassium Carbonate2×HCID 5925714-(4-Fluorophenyl)-2-thiazoleacetonitrileHCID 4569200ST509796462×

Product 1

HCID 673255584-(4-(4-Fluorophenyl)thiazol-2-yl)-2,2-dimethyltetrahydro-2H-pyran-4-carbonitrileYield 48%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-(4-(4-Fluorophenyl)thiazol-2-yl)acetonitrile (325 mg, 1.5 mmol), potassium carbonate (617 mg, 4.47 mmol), and 1-chloro-2-(2-chloroethoxy)-2-methylpropane (254 mg, 1.5 mmol) in DMF (5 mL) were microwaved at 160° C. for 5 min then 20 min. A second addition of potassium carbonate and 1-chloro-2-(2-chloroethoxy)-2-methylpropane was made and then the reaction was microwaved again for 30 min two times. The reaction was diluted with ethyl acetate and washed with water. The organic layer was dried over sodium sulfate and purified on silica using a gradient of 0-30% ethyl acetate/hexanes to afford 4-(4-(4-Fluorophenyl)thiazol-2-yl)-2,2-dimethyltetrahydro-2H-pyran-4-carbonitrile (228 mg, 48% yield). MS (ESI) m/z: Calculated for C17H17FN2OS: 316.10. found: 317.1 (M+H)+.

Workup

  1. custom20 min
  2. customthe reaction was microwaved again for 30 min two times
  3. washwashed with water
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. custompurified on silica using a gradient of 0-30% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-db78e97b820c4ecc8f96d8981e485791
Source dataset
uspto-grants-2014_12
Patent number
US08901156B2

Reaction notes

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