2,6-Dichloropyridine → 2-Chloro-6-(2-fluorophenylthio)pyridine

HRID 2077494Notes

Reaction equation

HRID 2077494 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[SH:8].[H-].[Na+].[Cl:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14](Cl)[N:13]=1>CN(C=O)C>[Cl:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([S:8][C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[F:1])[N:13]=1

Participants

5

Reactant 3

HCID 169892,6-DichloropyridineHCID 24758Sodium hydrideHCID 5202162-Fluorothiophenol

Product 1

HCID 575850522-Chloro-6-(2-fluorophenylthio)pyridineYield 35%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

2-Fluorothiophenol (Aldrich, St. Louis, Mo., Cat. No. 275379; 1.6 mL, 15 mmol) was dissolved in DMF (10 mL), and then NaH (0.45 g, 19 mmol) was added slowly to the mixture. After 1 hour, 2,6-dichloropyridine (Aldrich, St. Louis, Mo., Cat. No. 073707; 2.00 g, 14 mmol) was added and the mixture was heated in a pre-heated (70° C.) bath, and allowed to stir under inert atmosphere for 3 hours. The mixture was quenched with 1N NaOH and diluted with DCM. The organic layer was extracted with 4:1 DCM/MeOH (3×25 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. The crude residue was purified by ISCO Silica-Gel Chromatography (Teledyne ISCO, Lincoln, Nebr.) on a 120 gm column eluting with a solvent gradient of 1-30% DCM/Hexanes over 35 minutes to give 2-chloro-6-(2-fluorophenylthio)pyridine (1.13 g, 35% yield) as colorless oil. MS (ESI pos. ion) m/z: 240 (MH+). Calculated exact mass for C11H7ClFNS: 239.

Workup

  1. addition2.00 g, 14 mmol) was added
  2. temperaturethe mixture was heated in
  3. customThe mixture was quenched with 1N NaOH
  4. additiondiluted with DCM
  5. extractionThe organic layer was extracted with 4:1 DCM/MeOH (3×25 mL)
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude residue was purified by ISCO Silica-Gel Chromatography (Teledyne ISCO, Lincoln, Nebr.) on a 120 gm column
  10. washeluting with a solvent gradient of 1-30% DCM/Hexanes over 35 minutes

Sources & evidence

ORD record
ord-85147cbfe7544ead8eba35c374f881a4
Source dataset
uspto-grants-2011_04
Patent number
US07928140B2

Reaction notes

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