Phosphorus oxychloride → 3-Bromo-8-chloro-1,5-naphthyridine

HRID 1256183Notes

Reaction equation

HRID 1256183 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][C:5]2[CH:6]=[CH:7][CH:8]=[N+:9]([O-])[C:10]=2[CH:11]=1.P(Cl)(Cl)([Cl:15])=O>C(Cl)Cl>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([Cl:15])=[N:9]2)=[N:4][CH:3]=1.[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([Cl:15])=[CH:7][CH:8]=[N:9]2)=[N:4][CH:3]=1

Participants

5

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 57815209HCID 57815209, compound

Product 2

HCID 134591373-Bromo-8-chloro-1,5-naphthyridineHCID 583105447-Bromo-2-chloro-1,5-naphthyridine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

7.97 g (35.4 mmol, 1 eq) of 3-bromo-1,5-naphthyridine-5-oxide and 9.9 mL (106.2 mmol, 3 eq) of phosphorus oxychloride were introduced in 600 mL of methylene chloride. The mixture was stirred at reflux for 18 h. Methylene chloride was evaporated in part (¾). 1M aqueous NaOH solution was added carefully at 0° C. Aqueous layer was extracted with methylene chloride. Organic layers were dried over Na2SO4, filtered and evaporated to dryness. The residue was purified by column chromatography using methylene chloride as eluent. The solvent was evaporated to dryness to afford 1.97 g of 7-bromo-2-chloro-1,5-naphthyridine (white powder) with 22% yield and 4.16 g of 7-bromo-4-chloro-1,5-naphthyridine (white powder) with 48% yield.

Workup

  1. temperatureat reflux for 18 h
  2. customMethylene chloride was evaporated in part (¾)
  3. addition1M aqueous NaOH solution was added carefully at 0° C
  4. extractionAqueous layer was extracted with methylene chloride
  5. dry with materialOrganic layers were dried over Na2SO4
  6. filtrationfiltered
  7. customevaporated to dryness
  8. customThe residue was purified by column chromatography
  9. customThe solvent was evaporated to dryness

Sources & evidence

ORD record
ord-b9cf13659f0c4cb0b10eabddbf6632ce
Source dataset
uspto-grants-2013_06
Patent number
US08461178B2

Reaction notes

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