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

HRID 1621408

Reaction equation

HRID 1621408 reaction equation
[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][N:3]=1.[CH2:10](O)[CH2:11][OH:12].C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1.C(=O)(O)[O-].[Na+].O.CCOC(C)=O>[O:7]1[CH2:10][CH2:11][O:12][CH:6]1[C:5]1[CH:8]=[CH:9][C:2]([F:1])=[N:3][CH:4]=1

Participants

8

Reactant 3

HCID 174Ethylene GlycolHCID 6101p-Toluenesulfonic acidHCID 164142462-Fluoro-5-formylpyridine

Product 1

HCID 601557925-(1,3-Dioxolan-2-YL)-2-fluoropyridineYield 94%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
120 °C

Procedure

6-Fluoronicotinaldehyde (Asymchem Laboratories, Inc., Morrisville, N.C., 3.035 g, 24.26 mmol) was suspended in toluene (80 mL) and ethylene glycol (1.40 mL, 25.1 mmol) and p-toluenesulfonic acid (Acros Organics, Geel, Belgium, 12% in acetic acid, 0.15 mL) was added. The flask was fitted with a reflux condenser and placed in a preheated oil bath (120° C.) and stirred under nitrogen for 20 minutes. At this time, the reflux condenser was replaced with a Dean-Stark trap, and stirring was continued at 120° C. for 25 minutes. Then, the reaction was cooled and diluted with saturated sodium bicarbonate solution (20 mL) (before it had cooled to room temperature). The reaction was then diluted with water (20 mL) and EtOAc (30 mL). The layers were separated, and the aqueous phase was extracted with EtOAc. The organic extracts were combined, dried over sodium sulfate, filtered, concentrated, and purified on a silica gel filter (about 3 inches, 40:1 DCM/MeOH to 30:1 DCM/MeOH) to afford 5-(1,3-dioxolan-2-yl)-2-fluoropyridine (3.858 g), which was taken on to the next step. MS (ESI pos. ion) m/z 170 (M+H)+.

Workup

  1. customThe flask was fitted with a reflux condenser
  2. customplaced in a preheated oil bath
  3. stirringstirring
  4. waitwas continued at 120° C. for 25 minutes
  5. temperatureThen, the reaction was cooled
  6. customThe layers were separated
  7. extractionthe aqueous phase was extracted with EtOAc
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. custompurified on a silica gel
  12. filtrationfilter (about 3 inches, 40:1 DCM/MeOH to 30:1 DCM/MeOH)

Sources & evidence

ORD record
ord-a1e36680f0c14ae1a884cd414781ec2c
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Linked notes

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