Iodine → 3,5-Difluoro-4-iodopyridin-2-amine

HRID 710564Notes

Reaction equation

HRID 710564 reaction equation
C([Li])CCC.[NH2:6][C:7]1[C:12]([F:13])=[CH:11][C:10]([F:14])=[CH:9][N:8]=1.[I:15]I.S([O-])([O-])(=O)=S.[Na+].[Na+]>C1COCC1>[F:13][C:12]1[C:7]([NH2:6])=[N:8][CH:9]=[C:10]([F:14])[C:11]=1[I:15]

Participants

6

Reactant 4

HCID 807IodineHCID 24477Sodium ThiosulfateHCID 27832383,5-Difluoropyridin-2-amineHCID 178418339Butyllithium

Product 1

HCID 673650093,5-Difluoro-4-iodopyridin-2-amine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

n-Butyllithium (41 ml, 1.6 M solution in hexanes, 66 mmol) was added drop wise to a solution of 2-amino-3,5-difluoropyridine (3.4 g, 26 mmol) in THF (100 ml) at −78° C. The mixture was allowed to stir at that temperature for 1.5 hr, then a solution of iodine (20 g, 78 mmol) in THF (30 ml) was added. The mixture was stirred at −78° C. for 15 min, then it was allowed to warm to rt. Saturated aqueous sodium thiosulfate was added, and the mixture was extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, and concentrated. The residue was purified by silica gel chromatography (0-25% ethyl acetate in hexanes eluant) to provide the title compound. MS m/z: 297.9 (M+MeCN+1).

Workup

  1. stirringThe mixture was stirred at −78° C. for 15 min
  2. extractionthe mixture was extracted with ethyl acetate
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel chromatography (0-25% ethyl acetate in hexanes eluant)

Sources & evidence

ORD record
ord-221c19d763ac452d933d564f56899a29
Source dataset
uspto-grants-2015_11
Patent number
US09181238B2

Reaction notes

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