Dimethyl Sulfoxide → 5-(4-Fluoro-6-methylpyridin-2-yl)thiazole

HRID 523155Notes

Reaction equation

HRID 523155 reaction equation
Cl[C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([C:9]2[S:13][CH:12]=[N:11][CH:10]=2)[CH:3]=1.[F-:14].[Cs+].CS(C)=O>CCOC(C)=O>[F:14][C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([C:9]2[S:13][CH:12]=[N:11][CH:10]=2)[CH:3]=1

Participants

5

Reactant 3

HCID 679Dimethyl SulfoxideHCID 25953Cesium fluorideHCID 901180015-(4-Chloro-6-methylpyridin-2-yl)thiazole

Product 1

HCID 901179745-(4-Fluoro-6-methylpyridin-2-yl)thiazole

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

To a 2 dram vial equipped with a stir bar and charged with the entirety of 5-(4-chloro-6-methylpyridin-2-yl)thiazole from step 1 was added CsF (200 mg, 1.32 mmol) and DMSO (0.7 mL). The vial was capped and then placed in a 140° C. heating block with stirring for 16 h. The reaction mixture was transfered to a 125 mL separatory funnel and was diluted with EtOAc (50 mL). The solution was twice washed with brine:water (25 mL:25 mL); dried over MgSO4; filtered; then concentrated in vacuo to afford an amber solid residue. This material was subjected to silica gel chromatography (hexanes:EtOAc) to afford 5-(4-fluoro-6-methylpyridin-2-yl)thiazole as a colorless solid (7.1 mg, 21% over two steps). 1H-NMR (500 MHz, CDCl3) 8.84 (d, J=0.3 Hz, 1H), 8.32 (d, J=0.3 Hz, 1H), 7.22 (dd, J=9.3, 1.7 Hz, 1H), 6.82 (dd, J=9.2, 2.0 Hz, 1H), 2.59 (s, 3H); MS: MS m/z 195.2 (M++1).

Workup

  1. customTo a 2 dram vial equipped with a stir bar
  2. customThe vial was capped
  3. customplaced in a 140° C.
  4. temperatureheating block
  5. customThe reaction mixture was transfered to a 125 mL separatory funnel
  6. washThe solution was twice washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationthen concentrated in vacuo
  10. customto afford an amber solid residue

Sources & evidence

ORD record
ord-56bdfdaf005f4fa99fd746436957c877
Source dataset
uspto-grants-2016_05
Patent number
US09334279B2

Reaction notes

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