Ethylene Glycol → 5-(1,3-Dioxolan-2-YL)-2-fluoropyridine

HRID 561011

Reaction equation

HRID 561011 reaction equation
[F:1][C:2]1[N:7]=[CH:6][C:5]([CH:8]=[O:9])=[CH:4][CH:3]=1.[CH2:10](O)[CH2:11][OH:12].C1COCC1>C(Cl)(Cl)Cl.C(O)(C)C.O.O.[Cu](Cl)Cl>[O:9]1[CH2:10][CH2:11][O:12][CH:8]1[C:5]1[CH:4]=[CH:3][C:2]([F:1])=[N:7][CH:6]=1

Participants

6

Reactant 3

HCID 174Ethylene GlycolHCID 8028TetrahydrofuranHCID 164142462-Fluoro-5-formylpyridine

Product 1

HCID 601557925-(1,3-Dioxolan-2-YL)-2-fluoropyridineYield 39%

Reagents, catalysts & solvents 2

HCID 61482Cupric chloride dihydrateCatalystHCID 21906603Chloroform isopropyl alcoholSolvent

Conditions

Temperature
100 °C

Procedure

In a pressure vessel, combine 6-fluoro-pyridine-3-carbaldehyde (4 g, 32 mmol), ethylene glycol (3 g, 48 mmol), copper (II) chloride di-hydrate (0.56 g, 3.2 mmol) and THF (10 mL). Heat the mixture at 100° C. for 1 hour. Dilute the mixture with chloroform-isopropanol (3:1, 100 mL). Wash the organic phase with saturated aqueous sodium chloride and water. Dry the organic layer over sodium sulfate. Concentrate the solution in vacuo to brown oil. Purify by column chromatography (20% ethyl acetate in hexane) to afford the title compound (2.1 g, 39%) as a pale yellow oil. MS (ES) m/z 170 [M+1]+.

Workup

  1. customIn a pressure vessel, combine
  2. washWash the organic phase with saturated aqueous sodium chloride and water
  3. dry with materialDry the organic layer over sodium sulfate
  4. concentrationConcentrate the solution in vacuo to brown oil
  5. customPurify by column chromatography (20% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-f668c9cefe1e479794ff2c53df520d50
Source dataset
uspto-grants-2011_11
Patent number
US08063212B2

Linked notes

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