Water → 8-Ethyl-7-fluoro-2-(2-propen-1-yloxy)-1,5-naphthyridine

HRID 656904Notes

Reaction equation

HRID 656904 reaction equation
[CH2:1]([C:3]1[C:4]([F:14])=[CH:5][N:6]=[C:7]2[C:12]=1[NH:11][C:10](=[O:13])[CH:9]=[CH:8]2)[CH3:2].[H-].[Na+].[CH2:17](I)[CH:18]=[CH2:19].O>CN(C=O)C>[CH2:1]([C:3]1[C:4]([F:14])=[CH:5][N:6]=[C:7]2[C:12]=1[N:11]=[C:10]([O:13][CH2:19][CH:18]=[CH2:17])[CH:9]=[CH:8]2)[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 11166Allyl iodideHCID 24758Sodium hydrideHCID 688187718-Ethyl-7-fluoro-1,5-naphthyridin-2(1H)-one

Product 1

HCID 689954698-Ethyl-7-fluoro-2-(2-propen-1-yloxy)-1,5-naphthyridineYield 98%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

8-Ethyl-7-fluoro-1,5-naphthyridin-2(1H)-one (0.810 g, 4.22 mmol) was suspended in dry DMF (12.5 mL) under argon at 0° C., this was then treated with sodium hydride (0.371 g of a 60% w:w dispersion in oil, 2.2 eq.) added in portions. The suspension was allowed to warm to rt; after stirring for 30 mins at rt, the mixture was treated with allyl iodide (0.858 ml, 2.2 eq). It was then stirred for a further 30 mins before addition of water (10 ml). The mixture was then extracted with 10% MeOH/DCM (3×20 ml). The organic extracts were combined, dried over anhydrous sodium sulphate, filtered and evaporated under reduced pressure to give a brown oil. This residue was then purified by column chromatography on silica gel (50 g) eluting with 0-100% EtOAc in hexane gradient to give title compound as a brown oil (0.9588 g, 98%).

Workup

  1. additionw dispersion in oil, 2.2 eq.) added in portions
  2. extractionThe mixture was then extracted with 10% MeOH/DCM (3×20 ml)
  3. dry with materialdried over anhydrous sodium sulphate
  4. filtrationfiltered
  5. customevaporated under reduced pressure
  6. customto give a brown oil
  7. customThis residue was then purified by column chromatography on silica gel (50 g)
  8. washeluting with 0-100% EtOAc in hexane gradient

Sources & evidence

ORD record
ord-6d9afee54efc42689c1a33a24062e849
Source dataset
uspto-grants-2011_12
Patent number
US08071592B2

Reaction notes

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