Methanol → 4-(4-Methoxy-benzyl)-6-methyl-[1,4]oxazepane

HRID 515453Notes

Reaction equation

HRID 515453 reaction equation
[CH3:1][O:2][C:3]1[CH:18]=[CH:17][C:6]([CH2:7][N:8]2[CH2:14][CH:13]([CH3:15])[CH2:12][O:11][CH2:10][C:9]2=O)=[CH:5][CH:4]=1.CO.[OH-].[Na+]>O1CCCC1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]2[CH2:14][CH:13]([CH3:15])[CH2:12][O:11][CH2:10][CH2:9]2)=[CH:17][CH:18]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 14798Sodium HydroxideHCID 667185484-(4-Methoxy-benzyl)-6-methyl-[1,4]oxazepan-3-one

Product 1

HCID 667188184-(4-Methoxy-benzyl)-6-methyl-[1,4]oxazepaneYield 79%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 4-(4-methoxy-benzyl)-6-methyl-[1,4]oxazepan-3-one (4.35 g, 17.5 mmol) in tetrahydrofuran (10.0 ml) was added 1M borane-tetrahydrofuran complex in tetrahydrofuran (52.3 ml, 52.3 mmol) at 0° C. The mixture was stirred at room temperature for 4 hours. After cooling to 0° C., methanol (20 ml) and 6N sodium hydroxide aqueous solution (30 ml) was added carefully. The mixture was refluxed for 2 hours and cooled to room temperature. The organic solvent was removed under reduced pressure. The residue was partitioned between saturated ammonium chloride solution and ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography (eluant; hexane/ethyl acetate=1/1) to afford 4-(4-methoxy-benzyl)-6-methyl-[1,4]oxazepane as colorless oil (3.24 g, 79%).

Workup

  1. temperatureAfter cooling to 0° C.
  2. temperatureThe mixture was refluxed for 2 hours
  3. temperaturecooled to room temperature
  4. customThe organic solvent was removed under reduced pressure
  5. customThe residue was partitioned between saturated ammonium chloride solution and ethyl acetate
  6. washThe organic layer was washed with brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by silica gel column chromatography (eluant; hexane/ethyl acetate=1/1)

Sources & evidence

ORD record
ord-5ad442450c9c4bcea98fcd936d3082ce
Source dataset
uspto-grants-2015_08
Patent number
US09108957B2

Reaction notes

Loading…