Methanol, magnesium salt (2:1) → HCID 69058481, compound

HRID 1817375Notes

Reaction equation

HRID 1817375 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:24]=[CH:25][C:26]=1[F:27])[CH2:5][N:6]1[CH2:15][CH2:14][C:13]2[C:12]([C:16]([O:18][CH2:19]C)=[O:17])=[N:11][C:10]([OH:21])=[C:9]([OH:22])[C:8]=2[C:7]1=[O:23].[CH3:28][O-].[Mg+2].C[O-]>CN(C=O)C.CO>[Cl:1][C:2]1[CH:3]=[C:4]([CH:24]=[CH:25][C:26]=1[F:27])[CH2:5][N:6]1[CH2:15][CH2:14][C:13]2[C:8](=[C:9]([OH:22])[C:10](=[O:21])[N:11]([CH3:28])[C:12]=2[C:16]([O:18][CH3:19])=[O:17])[C:7]1=[O:23]

Participants

5

Reactant 2

HCID 164537Methanol, magnesium salt (2:1)HCID 178470321Ethyl 6-(3-chloro-4-fluorobenzyl)-3,4-dihydroxy-5-oxo-5,6,7,8-tetrahydro-2,6-naphthyridine-1-carboxylate

Product 1

HCID 69058481HCID 69058481, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
45 °C

Procedure

To a stirred suspension of ethyl 6-(3-chloro-4-fluorobenzyl)-3,4-dihydroxy-5-oxo-5,6,7,8-tetrahydro-2,6-naphthyridine-1-carboxylate (40 g) in DMF (200 mL) was added magnesium methoxide in methanol (100 mL). The mixture heated at 40-50° C. for 3 hours. The excess methanol distilled off, and methyl tosylate (18 mL) was added. The reaction mixture was heated at 50° C. overnight, then cooled to 25° C., and then quenched into 1N HCl (100 mL). The suspension stirred for 1 hour at ambient temperature. The product was isolated by filtration, and the filter cake washed with water (2×100 mL) and then dried on the filter under an atmosphere of nitrogen. The crude product was suspended in methanol (460 mL), heated at reflux temperature for 1 hour, and then allowed to cool to ambient temperature. The product was isolated by filtration and the filter cake washed with cold methanol (2×40 mL) and dried to give the title product.

Workup

  1. distillationThe excess methanol distilled off
  2. additionmethyl tosylate (18 mL) was added
  3. temperatureThe reaction mixture was heated at 50° C. overnight
  4. temperaturecooled to 25° C.
  5. customquenched into 1N HCl (100 mL)
  6. customThe product was isolated by filtration
  7. washthe filter cake washed with water (2×100 mL)
  8. customdried on the
  9. filtrationfilter under an atmosphere of nitrogen
  10. temperatureheated
  11. temperatureat reflux temperature for 1 hour
  12. temperatureto cool to ambient temperature
  13. customThe product was isolated by filtration
  14. washthe filter cake washed with cold methanol (2×40 mL)
  15. customdried

Sources & evidence

ORD record
ord-0f6956aa4cb440679c62580502f14c30
Source dataset
uspto-grants-2009_10
Patent number
US07598264B2

Reaction notes

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