Phosphorus oxychloride → 5-chloro-2-(trifluoromethyl)-1,8-Naphthyridine

HRID 1061741Notes

Reaction equation

HRID 1061741 reaction equation
[F:1][C:2]([F:15])([F:14])[C:3]1[N:12]=[C:11]2[C:6]([C:7](O)=[CH:8][CH:9]=[N:10]2)=[CH:5][CH:4]=1.P(Cl)(Cl)([Cl:18])=O>>[Cl:18][C:7]1[CH:8]=[CH:9][N:10]=[C:11]2[C:6]=1[CH:5]=[CH:4][C:3]([C:2]([F:15])([F:14])[F:1])=[N:12]2

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178516465HCID 178516465, compound

Product 1

HCID 222852765-chloro-2-(trifluoromethyl)-1,8-NaphthyridineYield 77%

Procedure

7-Trifluoromethyl[1,8]naphthyridin-4-ol (2.00 g, 9.34 mmol) was added in portions to phosphorus oxychloride with stirring at room temperature—a mild exotherm was observed. The mixture was stirred at room temperature under nitrogen overnight. The solvent was removed in vacuo, and saturated sodium hydrogencarbonate solution was added with ice-bath cooling to the residual material with stirring, until the pH of the mixture was ˜7. The mixture was extracted with dichloromethane (3×50 mL), then the combined organic layers were dried over magnesium sulfate, and were concentrated in vacuo. The crude product was purified by flash chromatography on silica gel, eluting with 25% ethyl acetate in dichloromethane, yielding 5-chloro-2-trifluoromethyl-[1,8]naphthyridine as an off-white solid (1.67 g, 77%). δH (360 MHz, CDCl3) 7.72 (1H, d, J 4.6), 7.96 (1H, d, J 8.8), 8.86 (1H, d, J 8.4), 9.15 (1H, d, J 4.6). m/z (ES+) 233, 235 [MH]+.

Workup

  1. stirringThe mixture was stirred at room temperature under nitrogen overnight
  2. customThe solvent was removed in vacuo, and saturated sodium hydrogencarbonate solution
  3. additionwas added with ice-bath
  4. temperaturecooling to the residual material
  5. stirringwith stirring, until the pH of the mixture
  6. extractionThe mixture was extracted with dichloromethane (3×50 mL)
  7. dry with materialthe combined organic layers were dried over magnesium sulfate
  8. concentrationwere concentrated in vacuo
  9. customThe crude product was purified by flash chromatography on silica gel
  10. washeluting with 25% ethyl acetate in dichloromethane

Sources & evidence

ORD record
ord-2cf9b9b77575441eae5f4dac567496fd
Source dataset
uspto-grants-2005_11
Patent number
US06960598B2

Reaction notes

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