Sulfuric Acid → 3-Fluoro-4-(4-hydroxypyrimidin-5-yl)picolinonitrile

HRID 871165Notes

Reaction equation

HRID 871165 reaction equation
[F:1][C:2]1[C:3]([C:14]#[N:15])=[N:4][CH:5]=[CH:6][C:7]=1[C:8]1[CH:9]=[N:10][CH:11]=[N:12][CH:13]=1.C(OO)(=[O:18])C.S(=O)(=O)(O)O.[OH-].[Na+]>CC(C)=O.C(Cl)Cl>[F:1][C:2]1[C:3]([C:14]#[N:15])=[N:4][CH:5]=[CH:6][C:7]=1[C:8]1[C:13]([OH:18])=[N:12][CH:11]=[N:10][CH:9]=1

Participants

7

Reactant 4

HCID 1118Sulfuric AcidHCID 6585Peracetic AcidHCID 14798Sodium HydroxideHCID 867304123-Fluoro-4-(pyrimidin-5-yl)picolinonitrile

Product 1

HCID 1785105763-Fluoro-4-(4-hydroxypyrimidin-5-yl)picolinonitrileYield 60.3%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 6344DichloromethaneSolvent

Procedure

To a vial charged with 3-fluoro-4-(pyrimidin-5-yl)picolinonitrile (0.400 g, 1.998 mmol) in acetone (Volume: 11.89 ml) were added peroxyacetic acid (0.841 ml, 4.00 mmol) and sulfuric acid (0.222 ml, 4.00 mmol). The reaction mixture was refluxed for 1 h, and then allowed to cool to room temperature. The reaction mixture was neutralized with 4 M NaOH and extracted with CH2Cl2 (5×). The organic phases were combined, dried over Na2SO4, filtered, and concentrated to afford a yellow residue. The crude material was dissolved in a minimal amount of CH2Cl2 to be chromatographed. Purification of the crude material by silica gel chromatography using an ISCO machine (40 g column, 40 mL/min, 0-25% MeOH in CH2Cl2 over 25 min, tr=16 min) gave the title compound (263 mg, 1.204 mmol, 60.3% yield) as a yellow solid. ESI MS (M+H)+=217.1.

Workup

  1. temperatureThe reaction mixture was refluxed for 1 h
  2. extractionextracted with CH2Cl2 (5×)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto afford a yellow residue
  7. customto be chromatographed
  8. customPurification of the crude material by silica gel chromatography
  9. customan ISCO machine (40 g column, 40 mL/min, 0-25% MeOH in CH2Cl2 over 25 min, tr=16 min)

Sources & evidence

ORD record
ord-1632b14c3e0b4a4a94305602a3b0e878
Source dataset
uspto-grants-2015_03
Patent number
US08969586B2

Reaction notes

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