Water → 1-(2,2-dimethoxyethyl)-7-fluoro-3,4-dihydro-1,5-naphthyridin-2(1H)-one

HRID 1804720Notes

Reaction equation

HRID 1804720 reaction equation
P([O-])([O-])([O-])=O.[K+].[K+].[K+].[F:9][C:10]1[CH:19]=[C:18]2[C:13]([CH2:14][CH2:15][C:16](=[O:20])[NH:17]2)=[N:12][CH:11]=1.Br[CH2:22][CH:23]([O:26][CH3:27])[O:24][CH3:25].O>CS(C)=O.C(O)(=O)C.C1(C)C=CC=CC=1>[CH3:25][O:24][CH:23]([O:26][CH3:27])[CH2:22][N:17]1[C:18]2[C:13](=[N:12][CH:11]=[C:10]([F:9])[CH:19]=2)[CH2:14][CH2:15][C:16]1=[O:20]

Participants

8

Reactant 4

HCID 962WaterHCID 62657Potassium Phosphate, Tribasic2×HCID 816722-Bromo-1,1-dimethoxyethane2×HCID 595107397-fluoro-3,4-dihydro-1,5-naphthyridin-2(1H)-one

Product 1

HCID 595107361-(2,2-dimethoxyethyl)-7-fluoro-3,4-dihydro-1,5-naphthyridin-2(1H)-oneYield 67.1%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 679Dimethyl SulfoxideSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a suspension of 49.8 g of potassium phosphate in 90 mL dimethyl sulfoxide, 30.0 g of 7-fluoro-3,4-dihydro-1,5-naphthyridin-2(1H)-one and 39.7 g of 2-bromo-1,1-dimethoxyethane were added, and the mixture was stirred at 100° C. for 3 hours. To the mixture, 7.7 g of potassium phosphate and 6.1 g of 2-bromo-1,1-dimethoxyethane were added, and the mixture was stirred for 1 hour at the same temperature. The reaction mixture was cooled to room temperature, and 120 mL of water and 120 mL of toluene were added thereto. The mixture was adjusted to pH 8.5 with acetic acid, and 3.0 g of activated carbon was added thereto. Insoluble matter was filtered out, and the filter residue was washed using 30 mL of toluene and 30 mL of water. The filtrate and the wash liquid were combined, the organic layer was separated, and the aqueous layer was extracted with 60 mL of toluene. The organic layer and the extract were combined to evaporate the solvent under reduced pressure, 90 mL of dibutyl ether was added thereto, and the mixture was cooled to −3° C. The solid product was obtained by filtration and washed using in the order of dibutyl ether and water to give 30.8 g of 1-(2,2-dimethoxyethyl)-7-fluoro-3,4-dihydro-1,5-naphthyridin-2(1H)-one as a light yellow solid.

Workup

  1. additionwere added
  2. stirringthe mixture was stirred for 1 hour at the same temperature
  3. temperatureThe reaction mixture was cooled to room temperature
  4. additionwas added
  5. filtrationInsoluble matter was filtered out
  6. washthe filter residue was washed
  7. customthe organic layer was separated
  8. extractionthe aqueous layer was extracted with 60 mL of toluene
  9. customto evaporate the solvent under reduced pressure, 90 mL of dibutyl ether
  10. additionwas added
  11. temperaturethe mixture was cooled to −3° C
  12. customThe solid product was obtained by filtration
  13. washwashed

Sources & evidence

ORD record
ord-b6e7c6371b9a4cbfa33cff8ad5b36051
Source dataset
uspto-grants-2013_01
Patent number
US08354426B2

Reaction notes

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