Trifluoroacetic acid → 7-fluoro-1-(2-hydroxy-2-methoxyethyl)-1,5-naphthyridin-2(1H)-one

HRID 385566Notes

Reaction equation

HRID 385566 reaction equation
[O:1]1[CH2:5]C[O:3][CH:2]1[CH2:6][N:7]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([F:17])[CH:15]=2)[CH:10]=[CH:9][C:8]1=[O:18].FC(F)(F)C(O)=O>>[F:17][C:14]1[CH:15]=[C:16]2[C:11]([CH:10]=[CH:9][C:8](=[O:18])[N:7]2[CH2:6][CH:2]([OH:3])[O:1][CH3:5])=[N:12][CH:13]=1

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acid3×HCID 578152081-(1,3-dioxolan-2-ylmethyl)-7-fluoro-1,5-naphthyridin-2(1H)-one

Product 1

HCID 578152967-fluoro-1-(2-hydroxy-2-methoxyethyl)-1,5-naphthyridin-2(1H)-oneYield 71.6%

Conditions

Temperature
85 °C

Procedure

To 2.2 g of 1-(1,3-dioxolan-2-ylmethyl)-7-fluoro-1,5-naphthyridin-2(1H)-one, 20 mL of an 80% aqueous trifluoroacetic acid solution was added, and the mixture was stirred at 80 to 90° C. for 3 hours. Thereto was added 10 mL of an 80% aqueous trifluoroacetic acid solution, and the mixture was stirred at 80 to 90° C. for 2 hours, then, 10 mL of an 80% aqueous trifluoroacetic acid solution was further added, and the mixture was stirred at the same temperature for 9 hours. The reaction mixture was cooled to room temperature, and the solvent was then distilled off under reduced pressure. To the resultant residue, a 2 mol/L aqueous sodium hydroxide solution was added and adjusted to pH 8.0, and chloroform and methanol were added thereto. The organic layer was separated, and the aqueous layer was extracted with a mixed solution of chloroform and methanol twice. The organic layer and the extract were combined, the resultant solution was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. Diethyl ether and hexane were added to the resultant residue, and the solid was filtered off to obtain 1.5 g of 7-fluoro-1-(2-hydroxy-2-methoxyethyl)-1,5-naphthyridin-2(1H)-one as a light brown solid.

Workup

  1. stirringthe mixture was stirred at 80 to 90° C. for 2 hours
  2. stirringthe mixture was stirred at the same temperature for 9 hours
  3. temperatureThe reaction mixture was cooled to room temperature
  4. distillationthe solvent was then distilled off under reduced pressure
  5. additionTo the resultant residue, a 2 mol/L aqueous sodium hydroxide solution was added
  6. additionwere added
  7. customThe organic layer was separated
  8. extractionthe aqueous layer was extracted with a mixed solution of chloroform and methanol twice
  9. dry with materialthe resultant solution was dried over anhydrous magnesium sulfate
  10. distillationthe solvent was distilled off under reduced pressure
  11. additionDiethyl ether and hexane were added to the resultant residue
  12. filtrationthe solid was filtered off

Sources & evidence

ORD record
ord-d32045b298cb46cf92755e84b49130f6
Source dataset
uspto-grants-2013_02
Patent number
US08367831B2

Reaction notes

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