Ethylene Glycol → 2-(1,3-Dioxolan-2-yl)-5-fluoro-3-nitropyridine

HRID 473424Notes

Reaction equation

HRID 473424 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N+:10]([O-:12])=[O:11])[C:5]([CH:8]=[O:9])=[N:6][CH:7]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.[CH2:24](O)[CH2:25][OH:26].O>C1(C)C=CC=CC=1>[O:9]1[CH2:24][CH2:25][O:26][CH:8]1[C:5]1[C:4]([N+:10]([O-:12])=[O:11])=[CH:3][C:2]([F:1])=[CH:7][N:6]=1

Participants

6

Reactant 4

HCID 174Ethylene GlycolHCID 962WaterHCID 6101p-Toluenesulfonic acidHCID 583186225-Fluoro-3-nitropicolinaldehyde

Product 1

HCID 583186012-(1,3-Dioxolan-2-yl)-5-fluoro-3-nitropyridine

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 5-fluoro-3-nitropicolinaldehyde (12.5 g, 73.48 mmol) in toluene (220 mL) were added p-toluene sulfonic acid (698 mg, 3.67 mmol) and ethylene glycol (20.7 mL, 367.43 mmol) at 25° C. The reaction mixture was heated to 120° C. for overnight and water was removed using dean-stark apparatus. Reaction mass was cooled to 25° C. Water was added to the reaction mass and extracted with EtOAc. Organic layer was washed with brine and dried over Na2SO4. The organic layer was concentrated in vacuo and purified by column chromatography on silica gel using 0-10% EtOAc in hexane to give 2-(1,3-dioxolan-2-yl)-5-fluoro-3-nitropyridine: 1H NMR (400 MHz, DMSO-d6): δ 4.02 (s, 4H), 6.22 (s, 1H), 8.939 (d, 1H, J=1.2 Hz); LC-MS (ESI) m/z 215.1 [M+H]+.

Workup

  1. customwater was removed
  2. customReaction mass
  3. temperaturewas cooled to 25° C
  4. extractionextracted with EtOAc
  5. washOrganic layer was washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationThe organic layer was concentrated in vacuo
  8. custompurified by column chromatography on silica gel using 0-10% EtOAc in hexane

Sources & evidence

ORD record
ord-8e91ba4c650748a5ab4f680fca55035b
Source dataset
uspto-grants-2014_01
Patent number
US08633313B2

Reaction notes

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