Potassium Phosphate, Tribasic → Tetrahydro-4-(2-methyl-4-nitrophenyl)-1,4-oxazepin-5(2H)-one

HRID 218527Notes

Reaction equation

HRID 218527 reaction equation
P([O-])([O-])([O-])=O.[K+].[K+].[K+].[O:9]1[CH2:15][CH2:14][C:13](=[O:16])[NH:12][CH2:11][CH2:10]1.I[C:18]1[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][C:19]=1[CH3:27].CN(C)CCN>[Cu]I.O1CCOCC1>[CH3:27][C:19]1[CH:20]=[C:21]([N+:24]([O-:26])=[O:25])[CH:22]=[CH:23][C:18]=1[N:12]1[C:13](=[O:16])[CH2:14][CH2:15][O:9][CH2:10][CH2:11]1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 66053N,N-DimethylethylenediamineHCID 792252-Iodo-5-nitrotolueneHCID 70230201,4-Oxazepan-5-one

Product 1

HCID 59586730Tetrahydro-4-(2-methyl-4-nitrophenyl)-1,4-oxazepin-5(2H)-one

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

3.32 g (15.6 mmol) of potassium phosphate are mixed with 0.5 g (2.6 mmol) of copper(I) iodide in a round-bottom flask, and baked out and filled with argon in repeated alternation. Subsequently, 10 ml of anhydrous dioxane, 1.5 g (13.0 mmol) of 1,4-oxazepan-5-one, 3.43 g (13.0 mmol) of 1-iodo-2-methyl-4-nitrobenzene and 0.46 g (5.21 mmol) of N,N-dimethylethylenediamine are added, and the mixture is heated to 110° C. for 15 h. The mixture is allowed to cool and filtered through silica gel, and the silica gel is washed with dioxane. The combined filtrates are concentrated to dryness under reduced pressure. The residue is dissolved in acetonitrile and purified by preparative HPLC with a gradient of water and acetonitrile. The product fractions are combined and concentrated to dryness under reduced pressure. This affords 430 mg (13% of theory) of the desired product.

Workup

  1. additionfilled with argon in repeated alternation
  2. temperatureto cool
  3. filtrationfiltered through silica gel
  4. washthe silica gel is washed with dioxane
  5. concentrationThe combined filtrates are concentrated to dryness under reduced pressure
  6. dissolutionThe residue is dissolved in acetonitrile
  7. custompurified by preparative HPLC with a gradient of water and acetonitrile
  8. concentrationconcentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-81e35fe8f72c40a28cb1812900cc756b
Source dataset
uspto-grants-2012_06
Patent number
US08198267B2

Reaction notes

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