Sodium Azide → 4-Azido-6-bromo-2-chloro-3-(difluoromethoxy)pyridine

HRID 407217

Reaction equation

HRID 407217 reaction equation
Br[C:2]1[CH:7]=[C:6]([Br:8])[N:5]=[C:4]([Cl:9])[C:3]=1[O:10][CH:11]([F:13])[F:12].[N-:14]=[N+:15]=[N-:16].[Na+]>CN(C=O)C>[N:14]([C:2]1[CH:7]=[C:6]([Br:8])[N:5]=[C:4]([Cl:9])[C:3]=1[O:10][CH:11]([F:13])[F:12])=[N+:15]=[N-:16]

Participants

4

Reactant 2

HCID 33557Sodium AzideHCID 866754024,6-Dibromo-2-chloro-3-(difluoromethoxy)pyridine

Product 1

HCID 866754034-Azido-6-bromo-2-chloro-3-(difluoromethoxy)pyridineYield 48.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

4,6-Dibromo-2-chloro-3-(difluoromethoxy)pyridine (780 mg, 2.312 mmol) was dissolved in DMF (5 mL), and sodium azide (180 mg, 2.77 mmol) was added. The reaction mixture was heated at 65° C. for 2 h and the progress of the reaction was checked by liquid chromatography-mass spectrometry (LC-MS). The reaction appeared to be mostly complete. The product was partitioned between Et2O and H2O. The aqueous phase was then extracted twice more with Et2O. The organic extracts were combined, diluted with petroleum ether, washed twice with H2O, dried, and concentrated. The product was purified by column chromatography (SiO2, EtOAc/hexane gradient) to yield 4-azido-6-bromo-2-chloro-3-(difluoromethoxy)-pyridine (0.335 g, 48.4%): 1H NMR (300 MHz, CDCl3) δ 7.26 (s, 1H), 6.59 (t, J=73.6, 1H).

Workup

  1. customThe product was partitioned between Et2O and H2O
  2. extractionThe aqueous phase was then extracted twice more with Et2O
  3. additiondiluted with petroleum ether
  4. washwashed twice with H2O
  5. customdried
  6. concentrationconcentrated
  7. customThe product was purified by column chromatography (SiO2, EtOAc/hexane gradient)

Sources & evidence

ORD record
ord-936a03b1ed174943acf86b9cf6c1e710
Source dataset
uspto-grants-2014_06
Patent number
US08754229B2

Linked notes

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