Water → 1-(1,3-dioxolan-2-ylmethyl)-7-fluoro-1,5-naphthyridin-2(1H)-one

HRID 1510615Notes

Reaction equation

HRID 1510615 reaction equation
[F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8](=[O:12])[NH:9]2)=[N:4][CH:3]=1.[H-].[Na+].Br[CH2:16][CH:17]1[O:21][CH2:20][CH2:19][O:18]1.O>CN(C)C=O.C(OCC)(=O)C>[O:18]1[CH2:19][CH2:20][O:21][CH:17]1[CH2:16][N:9]1[C:10]2[C:5](=[N:4][CH:3]=[C:2]([F:1])[CH:11]=2)[CH:6]=[CH:7][C:8]1=[O:12]

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 780681,3-Dioxolane, 2-(bromomethyl)-HCID 469008017-Fluoro-1,5-naphthyridin-2(1H)-one

Product 1

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

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
55 °C

Procedure

To a suspension of 0.32 g of 7-fluoro-1,5-naphthyridin-2(1H)-one in 3 mL of N,N-dimethylformamide, 0.12 g of 60% sodium hydride was added at room temperature, and the mixture was stirred at 50 to 60° C. for 1 hour. Thereto was added 0.60 mL of 2-bromomethyl-1,3-dioxolan, the temperature was increased to 85 to 95° C., and the reaction mixture was stirred for 4 hours. The reaction mixture was cooled to room temperature, and water and ethyl acetate were then added thereto. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. 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. To the resultant residue, chloroform was added, the solid was filtered off and purified by flash silica gel column chromatography using gradient elution with hexane:ethyl acetate=100:0 to 30:70 to obtain 0.23 g of 1-(1,3-dioxolan-2-ylmethyl)-7-fluoro-1,5-naphthyridin-2(1H)-one as a light yellow solid.

Workup

  1. additionwas added at room temperature
  2. temperaturethe temperature was increased to 85 to 95° C.
  3. stirringthe reaction mixture was stirred for 4 hours
  4. temperatureThe reaction mixture was cooled to room temperature
  5. customThe organic layer was separated
  6. extractionthe aqueous layer was extracted with ethyl acetate
  7. dry with materialthe resultant solution was dried over anhydrous magnesium sulfate
  8. distillationthe solvent was distilled off under reduced pressure
  9. additionTo the resultant residue, chloroform was added
  10. filtrationthe solid was filtered off
  11. custompurified by flash silica gel column chromatography
  12. washelution with hexane

Sources & evidence

ORD record
ord-24483b024f584fe285b8247d8bb349fc
Source dataset
uspto-grants-2012_07
Patent number
US08211908B2

Reaction notes

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