Nitrogen → 2-Fluoro-5-(thiazol-5-yl)benzonitrile

HRID 1891492Notes

Reaction equation

HRID 1891492 reaction equation
C([Sn](CCCC)(CCCC)[C:6]1[S:10][CH:9]=[N:8][CH:7]=1)CCC.[F:19][C:20]1[CH:27]=[CH:26][C:25](I)=[CH:24][C:21]=1[C:22]#[N:23].N#N>C1COCC1>[F:19][C:20]1[CH:27]=[CH:26][C:25]([C:6]2[S:10][CH:9]=[N:8][CH:7]=2)=[CH:24][C:21]=1[C:22]#[N:23]

Participants

5

Reactant 3

HCID 947NitrogenHCID 27632575-(Tributylstannyl)-1,3-thiazoleHCID 27789282-Fluoro-5-iodobenzonitrile

Product 1

HCID 671916142-Fluoro-5-(thiazol-5-yl)benzonitrileYield 82%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
85 °C

Procedure

To 5-(tributylstannyl)thiazole (1.00 g, 2.7 mmol) in THF (10 mL) was added 2-fluoro-5-iodobenzonitrile (0.791 g, 3.2 mmol). The solution was degassed with N2 and bis(triphenylphosphine)palladium(II) chloride Pd(Ph)2Cl2 (0.187 g, 0.27 mmol) was added. The solution was further degassed for five minutes before heating to 85° C. for 2 h. Upon cooling, the reaction mixture was diluted with saturated NaHCO3 and washed with EA (3×50 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated. The crude product was purified by chromatography (10% EA/Hexanes) to afford 0.450 g (82%) of 2-fluoro-5-(thiazol-5-yl)benzonitrile THZ INT-3 as a tan solid. LCMS-ESI (m/z) calculated for C10H5FN2S: 204.2; found 205.0 [M+H]+, tR=3.00 min.

Workup

  1. additionwas added
  2. customThe solution was further degassed for five minutes
  3. temperatureUpon cooling
  4. additionthe reaction mixture was diluted with saturated NaHCO3
  5. washwashed with EA (3×50 mL)
  6. dry with materialThe combined organic layers were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was purified by chromatography (10% EA/Hexanes)

Sources & evidence

ORD record
ord-532c777ab778463fbccc212e606e4a00
Source dataset
uspto-grants-2013_08
Patent number
US08507538B2

Reaction notes

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