Methyl iodide → Methyl 6-(3-chloro-4-fluorobenzyl)-4-methoxy-2-methyl-3,5-dioxo-2,3,5,6,7,8-hexahydro-2,6-naphthyridine-1-carboxylate

HRID 1817333Notes

Reaction equation

HRID 1817333 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:8](=[C:9]([OH:22])[C:10](=[O:21])[N:11]([CH3:20])[C:12]=2[C:16]([O:18][CH3:19])=[O:17])[C:7]1=[O:23].[C:28](=O)([O-])[O-].[Cs+].[Cs+].IC>CN(C=O)C>[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]([O:22][CH3:28])[C:10](=[O:21])[N:11]([CH3:20])[C:12]=2[C:16]([O:18][CH3:19])=[O:17])[C:7]1=[O:23]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 10796Cesium carbonateHCID 69058481HCID 69058481, compound

Product 1

HCID 69058384Methyl 6-(3-chloro-4-fluorobenzyl)-4-methoxy-2-methyl-3,5-dioxo-2,3,5,6,7,8-hexahydro-2,6-naphthyridine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of methyl 6-(3-chloro-4-fluorobenzyl)-4-hydroxy-2-methyl-3,5-dioxo-2,3,5,6,7,8-hexahydro-2,6-naphthyridine-1-carboxylate (7.25 g, 18 mmol) in anhydrous DMF (75 mL) was added cesium carbonate (5.98 g, 18 mmol) and iodomethane (2.86 mL, 46 mmol). The reaction was stirred at room temperature overnight, and LCMS showed 70% completion. The reaction was heated to 50° C. for 7 hours and then allowed to stir at room temperature again overnight. LCMS indicated completion. The reaction was concentrated to dryness, and the resulting residue was dissolved in chloroform. The solution was extracted twice with saturated Na2SO3 solution, dried over sodium sulfate, filtered, and evaporated to afford a dark brown oil.

Workup

  1. temperatureThe reaction was heated to 50° C. for 7 hours
  2. stirringto stir at room temperature again overnight
  3. concentrationThe reaction was concentrated to dryness
  4. dissolutionthe resulting residue was dissolved in chloroform
  5. extractionThe solution was extracted twice with saturated Na2SO3 solution
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customto afford a dark brown oil

Sources & evidence

ORD record
ord-5d532b35e6894c3db365dfc736f86064
Source dataset
uspto-grants-2009_10
Patent number
US07598264B2

Reaction notes

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