Methyl iodide → HCID 69058481, compound

HRID 1817332Notes

Reaction equation

HRID 1817332 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:23]=[CH:24][C:25]=1[F:26])[CH2:5][N:6]1[CH2:15][CH2:14][C:13]2[C:12]([C:16]([O:18][CH3:19])=[O:17])=[N:11][C:10]([OH:20])=[C:9]([OH:21])[C:8]=2[C:7]1=[O:22].[CH3:27][O-].C[O-].[Mg+2].IC>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:23]=[CH:24][C:25]=1[F:26])[CH2:5][N:6]1[CH2:15][CH2:14][C:13]2[C:8](=[C:9]([OH:21])[C:10](=[O:20])[N:11]([CH3:27])[C:12]=2[C:16]([O:18][CH3:19])=[O:17])[C:7]1=[O:22]

Participants

5

Reactant 3

HCID 6328Methyl iodide2×HCID 164537Methanol, magnesium salt (2:1)HCID 178499134HCID 178499134, compound

Product 1

HCID 69058481HCID 69058481, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of methyl 6-(3-chloro-4-fluorobenzyl)-3,4-dihydroxy-5-oxo-5,6,7,8-tetrahydro-2,6-naphthyridine-1-carboxylate (18.00 g, 47 mmol) in DMF (200 mL) was added magnesium methylate (96.08 mL, 95 mmol), and the reaction was warmed for 1 hour and cooled. The reaction was treated with iodomethane (17.66 mL, 283 mmol) and stirred at 45° C. overnight. At this time, LCMS showed the reaction incomplete, and an additional equivalent of iodomethane (2.95 mL, 48 mmol) was added. The reaction was again stirred for 4 hours. The solvent was removed in vacuo, and the resulting oil was partitioned between chloroform and 1N HCl. The aqueous layer was washed twice more with chloroform. The organic fractions were extracted with 10% sodium bisulfite, and the bisulfite layer was washed twice with chloroform. The combined organic layers were washed with 5% aqueous HCl and brine, dried over sodium sulfate and concentrated in vacuo to afford the product as a black oil. This material appears quite clean by NMR and HPLC, but is highly colored.

Workup

  1. temperaturethe reaction was warmed for 1 hour
  2. temperaturecooled
  3. additionwas added
  4. stirringThe reaction was again stirred for 4 hours
  5. customThe solvent was removed in vacuo
  6. customthe resulting oil was partitioned between chloroform and 1N HCl
  7. washThe aqueous layer was washed twice more with chloroform
  8. extractionThe organic fractions were extracted with 10% sodium bisulfite
  9. washthe bisulfite layer was washed twice with chloroform
  10. washThe combined organic layers were washed with 5% aqueous HCl and brine
  11. dry with materialdried over sodium sulfate
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3dc73c1fd1c94fe6b55769fe2911918e
Source dataset
uspto-grants-2009_10
Patent number
US07598264B2

Reaction notes

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