Dimethylformamide → 7-(difluoromethoxy)-1-(1,3-dioxolan-2-ylmethyl)-1,5-naphthyridin-2(1H)-one

HRID 1510718Notes

Reaction equation

HRID 1510718 reaction equation
[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[CH2:6][N:7]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([OH:17])[CH:15]=2)[CH:10]=[CH:9][C:8]1=[O:18].[OH-].[Na+].CN(C)C=O.Cl[CH:27]([F:29])[F:28]>C1(C)C=CC=CC=1.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O>[F:28][CH:27]([F:29])[O: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]2[O:1][CH2:5][CH2:4][O:3]2)=[N:12][CH:13]=1

Participants

8

Reactant 4

HCID 6228Dimethylformamide2×HCID 6372Chlorodifluoromethane2×HCID 14798Sodium HydroxideHCID 578153801-(1,3-dioxolan-2-ylmethyl)-7-hydroxy-1,5-naphthyridin-2(1H)-one

Product 1

HCID 578154437-(difluoromethoxy)-1-(1,3-dioxolan-2-ylmethyl)-1,5-naphthyridin-2(1H)-one

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 962WaterSolventHCID 1140TolueneSolvent2×

Procedure

To a suspension of 0.15 g of 1-(1,3-dioxolan-2-ylmethyl)-7-hydroxy-1,5-naphthyridin-2(1H)-one in 1.5 mL of toluene, 1 mL of a 40% aqueous sodium hydroxide solution, 97 mg of tetrabutylammonium bromide and 0.25 mL of an N,N-dimethylformamide solution of 10 mol/L chloro(difluoro)methane were added, the mixture was stirred for 50 minutes, then, thereto was added 1 mL of an N,N-dimethylformamide solution of 10 mol/L chloro(difluoro)methane, and the mixture was stirred for 3 hours 40 minutes. Water and toluene were added to the reaction mixture, the organic layer was separated, and the aqueous layer was extracted with toluene. The organic layer and the extract were combined, the resultant solution was washed sequentially with water and a saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain 95 mg of 7-(difluoromethoxy)-1-(1,3-dioxolan-2-ylmethyl)-1,5-naphthyridin-2(1H)-one as a light brown solid.

Workup

  1. additionwere added
  2. stirringthe mixture was stirred for 3 hours 40 minutes
  3. customthe organic layer was separated
  4. extractionthe aqueous layer was extracted with toluene
  5. washthe resultant solution was washed sequentially with water
  6. dry with materiala saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate
  7. distillationthe solvent was distilled off under reduced pressure

Sources & evidence

ORD record
ord-84948c3a5c0940d6ab8bc2594ab87e57
Source dataset
uspto-grants-2012_07
Patent number
US08211908B2

Reaction notes

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