Diethyl Ether → 2,6-Difluoro-3-neopentylpyridine

HRID 20032Notes

Reaction equation

HRID 20032 reaction equation
[CH2:1]([Mg]Cl)[C:2]([CH3:5])([CH3:4])[CH3:3].CCOCC.[F:13][C:14]1[C:19](I)=[CH:18][CH:17]=[C:16]([F:21])[N:15]=1.[NH4+].[Cl-]>C1COCC1.[Cl-].[Zn+2].[Cl-]>[F:13][C:14]1[C:19]([CH2:1][C:2]([CH3:5])([CH3:4])[CH3:3])=[CH:18][CH:17]=[C:16]([F:21])[N:15]=1

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 25517Ammonium ChlorideHCID 197684332,6-Difluoro-3-iodopyridineHCID 178418809HCID 178418809, compound

Product 1

HCID 673053062,6-Difluoro-3-neopentylpyridine

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

To a 500 mL RBF was added neopentylmagnesium chloride, 111.0M in ether (28.0 ml, 28 mmol) and an ice bath. After cooling, zinc(II) chloride, 0.5M in THF (56.0 ml, 28 mmol) was added dropwise. The cooling bath was removed and after stirring for 45 minutes, Reactant 1 (0.26 g, 0.32 mmol) was added followed by 2,6-difluoro-3-iodopyridine (2.74 g, 8.0 mmol) in THF (10 mL), which was added dropwise. The yellow solution was then heated to 60° C. After stirring overnight the reaction was allowed to cool and sat'd. NH4Cl was added cautiously. The reaction mixture was partitioned between EtOAc/Water. The aqueous layer was extracted with EtOAc (50 mL) and the combined organic layers washed with brine and concentrated in vacuo. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Redi-Sep® pre-packed silica gel column (40 g), eluting with 1% EtOAc in hexane, to provide 2,6-difluoro-3-neopentylpyridine as a colorless oil. MS m/z: 186 (M+1).

Workup

  1. temperatureAfter cooling
  2. customThe cooling bath was removed
  3. additionwas added dropwise
  4. stirringAfter stirring overnight the reaction
  5. temperatureto cool
  6. customThe reaction mixture was partitioned between EtOAc/Water
  7. extractionThe aqueous layer was extracted with EtOAc (50 mL)
  8. washthe combined organic layers washed with brine
  9. concentrationconcentrated in vacuo
  10. customchromatographed through a Redi-Sep® pre-packed silica gel column (40 g)
  11. washeluting with 1% EtOAc in hexane

Sources & evidence

ORD record
ord-a016c414375f412686526470b1e9bbba
Source dataset
uspto-grants-2010_06
Patent number
US07745484B2

Reaction notes

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