Dimethyl Sulfoxide → 4-Fluoro-6-(4-isopropoxyphenyl)-2,2'-bipyridine

HRID 523151Notes

Reaction equation

HRID 523151 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH:15]([CH3:17])[CH3:16])=[CH:10][CH:9]=2)[N:5]=[C:4]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=2)[CH:3]=1.[F-:24].[Cs+].CS(C)=O.CCCCCC>CCOC(C)=O>[F:24][C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH:15]([CH3:17])[CH3:16])=[CH:10][CH:9]=2)[N:5]=[C:4]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=2)[CH:3]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8058HexaneHCID 25953Cesium fluorideHCID 901179274-Chloro-6-(4-isopropoxyphenyl)-2,2'-bipyridine2×

Product 1

HCID 901180754-Fluoro-6-(4-isopropoxyphenyl)-2,2'-bipyridine

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

To a 2 dram vial equipped with a stir bar and charged with 4-chloro-6-(4-isopropoxyphenyl)-2,2′-bipyridine (all material from step 1) was added cesium fluoride (200 mg, 1.32 mmol) and DMSO (0.7 mL). The vial was sealed with a septum cap and then placed in a 140° C. heating block with stirring for 18 h. The reaction mixture was allowed to cool to room temperature. The mixture was transfered to a 125 mL separatory funnel and was diluted with EtOAc (50 mL) and then twice washed with water:brine (25 mL:25 mL). The organic solution was dried over MgSO4; filtered; then concentrated in vacuo to afford an amber solid residue which was subjected to silica gel chromatography (hexane:EtOAc) to afford 4-fluoro-6-(4-isopropoxyphenyl)-2,2′-bipyridine as a colorless solid (16 mg, 29% over two steps). 1H-NMR (400 MHz, CDCl3) δ 8.72-8.67 (m, 1H), 8.62 (dt, J=7.8, 1.0 Hz, 1H), 8.10-8.05 (m, 3H), 7.86 (td, J=7.8, 1.8 Hz, 1H), 7.41 (dd, J=10.0, 2.3 Hz, 1H), 7.35 (ddd, J=7.5, 4.8, 1.3 Hz, 1H), 7.04-6.99 (m, 2H), 4.66 (spt, J=6.1 Hz, 1H), 1.40 (d, J=6.0 Hz, 6H); MS: MS m/z 309.2 (M++1).

Workup

  1. customTo a 2 dram vial equipped with a stir bar
  2. customThe vial was sealed with a septum
  3. customcap
  4. customplaced in a 140° C.
  5. temperatureheating block
  6. customThe mixture was transfered to a 125 mL separatory funnel
  7. washtwice washed with water
  8. dry with materialThe organic solution was dried over MgSO4
  9. filtrationfiltered
  10. concentrationthen concentrated in vacuo
  11. customto afford an amber solid residue which

Sources & evidence

ORD record
ord-c6a28001cb614484b93ed38de2a902e3
Source dataset
uspto-grants-2016_05
Patent number
US09334279B2

Reaction notes

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