Potassium Carbonate → 1-(2,2-dimethoxyethyl)-7-fluoro-1,5-naphthyridin-2(1H)-one

HRID 1804721Notes

Reaction equation

HRID 1804721 reaction equation
[CH3:1][O:2][CH:3]([O:17][CH3:18])[CH2:4][N:5]1[C:14]2[C:9](=[N:10][CH:11]=[C:12]([F:15])[CH:13]=2)[CH2:8][CH2:7][C:6]1=[O:16].BrN1C(=O)CCC1=O.C(=O)([O-])[O-].[K+].[K+].[OH-].[Na+]>ClC1C=CC=CC=1.N(C(C)(CC(OC)(C)C)C#N)=NC(C)(CC(C)(OC)C)C#N.O>[CH3:18][O:17][CH:3]([O:2][CH3:1])[CH2:4][N:5]1[C:14]2[C:9](=[N:10][CH:11]=[C:12]([F:15])[CH:13]=2)[CH:8]=[CH:7][C:6]1=[O:16]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 67184N-bromobutanimideHCID 595107361-(2,2-dimethoxyethyl)-7-fluoro-3,4-dihydro-1,5-naphthyridin-2(1H)-one

Product 1

HCID 595107441-(2,2-dimethoxyethyl)-7-fluoro-1,5-naphthyridin-2(1H)-oneYield 82.7%

Reagents, catalysts & solvents 3

HCID 858672,2'-Azobis(2,4-dimethyl-4-methoxyvaleronitrile)CatalystHCID 962WaterSolventHCID 7964ChlorobenzeneSolvent

Procedure

To a suspension of 5.0 g of 1-(2,2-dimethoxyethyl)-7-fluoro-3,4-dihydro-1,5-naphthyridin-2(1H)-one, 5.3 g of N-bromosuccinimide and 3.0 g of potassium carbonate in 30 mL of chlorobenzene, 0.12 g of 2,2′-azobis(4-methoxy-2,4-dimethylvaleronitrile) was added three times hourly at 50 to 60° C. under a nitrogen atmosphere. After stirring the reaction mixture for 1 hour at the same temperature, 10 mL of water was added thereto, and the mixture was adjusted to pH 12.6 using a 20% sodium hydroxide solution. The organic layer was separated and washed with 15 mL of water. The aqueous layer was extracted with 15 mL of toluene. The organic layer and the extract were combined to evaporate the solvent under reduced pressure. To the obtained residue, 2 mL of chlorobenzene and 6 mL of cyclohexane were added, the mixture was stirred for 30 minutes under ice cooling, and the solid product was obtained by filtration and washed with cyclohexane to give 4.1 g of 1-(2,2-dimethoxyethyl)-7-fluoro-1,5-naphthyridin-2(1H)-one as a light yellow solid.

Workup

  1. additionwas added three times hourly at 50 to 60° C. under a nitrogen atmosphere
  2. additionwas added
  3. customThe organic layer was separated
  4. washwashed with 15 mL of water
  5. extractionThe aqueous layer was extracted with 15 mL of toluene
  6. customto evaporate the solvent under reduced pressure
  7. additionTo the obtained residue, 2 mL of chlorobenzene and 6 mL of cyclohexane were added
  8. customthe solid product was obtained by filtration
  9. washwashed with cyclohexane

Sources & evidence

ORD record
ord-bb90db7725b24cfa9479b812a36e71eb
Source dataset
uspto-grants-2013_01
Patent number
US08354426B2

Reaction notes

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