Ethanol → 7-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-4-((R)-1-phenyl-ethyl)-[1,4]oxazepane

HRID 515481Notes

Reaction equation

HRID 515481 reaction equation
[C:1]1([C@H:7]([N:9]2[CH2:15][CH2:14][CH:13]([C:16]3[CH:23]=[CH:22][C:19]([C:20]#[N:21])=[CH:18][CH:17]=3)[O:12][CH2:11][CH2:10]2)[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.O.Cl.[NH2:26]O.C(=O)(O)[O-].[Na+].[CH2:33]([OH:35])[CH3:34]>>[CH3:34][C:33]1[O:35][N:26]=[C:20]([C:19]2[CH:18]=[CH:17][C:16]([CH:13]3[O:12][CH2:11][CH2:10][N:9]([C@@H:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[CH3:8])[CH2:15][CH2:14]3)=[CH:23][CH:22]=2)[N:21]=1

Participants

6

Reactant 5

HCID 702EthanolHCID 962WaterHCID 443297Hydroxyamine hydrochlorideHCID 516892Sodium BicarbonateHCID 672813254-[4-((R)-1-phenyl-ethyl)-[1,4]oxazepan-7-yl]-benzonitrile

Product 1

HCID 672833297-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-4-((R)-1-phenyl-ethyl)-[1,4]oxazepane

Conditions

Temperature
80 °C

Procedure

To a mixture of 4-[4-((R)-1-phenyl-ethyl)-[1,4]oxazepan-7-yl]-benzonitrile (diastereomer type A) (0.68 g, 2.2 mmol) in ethanol (5 mL) and water (3 mL) was added hydroxylamine hydrochloride (0.46 g, 6.6 mmol) and sodium bicarbonate (1.20 g, 11 mmol) at room temperature and the resulting mixture was heated to 80° C. After stirring for 2 hours, the reaction mixture was evaporated for removal of ethanol and diluted with water and chloroform. The organic phase was separated from aqueous phase and dried over anhydrous sodium sulfate. After concentration, half of the residue (0.39 g) was dissolved in xylene (3 mL) and dimethylacetamide dimethylacetal was added at room temperature. The mixture was refluxed for 3 hours and concentrated. The residual material was purified by flash column chromatography on silica gel to yield 7-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-4-((R)-1-phenyl-ethyl)-[1,4]oxazepane (diastereomer type A) (0.33 g, 0.92 mmol, 83%).

Workup

  1. customthe reaction mixture was evaporated for removal of ethanol
  2. additiondiluted with water and chloroform
  3. customThe organic phase was separated from aqueous phase
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationAfter concentration, half of the residue (0.39 g)
  6. dissolutionwas dissolved in xylene (3 mL)
  7. additiondimethylacetamide dimethylacetal was added at room temperature
  8. temperatureThe mixture was refluxed for 3 hours
  9. concentrationconcentrated
  10. customThe residual material was purified by flash column chromatography on silica gel

Sources & evidence

ORD record
ord-9ded372dcac94746a0d0adacc19e6ae0
Source dataset
uspto-grants-2015_08
Patent number
US09108957B2

Reaction notes

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