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

HRID 515484Notes

Reaction equation

HRID 515484 reaction equation
[C:1]1([C@H:7]([N:9]2[CH2:15][CH2:14][CH:13]([C:16]3[CH:24]=[CH:23][C:19]([C:20]([NH2:22])=[O: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.[OH-].[Na+].Cl.[NH2:28]O.[C:30](O)(=O)[CH3:31]>COC(OC)(N(C)C)C.O>[CH3:31][C:30]1[N:22]=[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:24][CH:23]=2)[O:21][N:28]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 443297Hydroxyamine hydrochlorideHCID 672820504-[4-((R)-1-phenyl-ethyl)-[1,4]oxazepan-7-yl]-benzamide

Product 1

HCID 672822577-[4-(3-methyl-[1,2,4]oxadiazol-5-yl)-phenyl]-4-((R)-1-phenyl-ethyl)-[1,4]oxazepane

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 878351,1-Dimethoxyethyl(dimethyl)amineSolvent

Conditions

Temperature
110 °C

Procedure

4-[4-((R)-1-Phenyl-ethyl)-[1,4]oxazepan-7-yl]-benzamide (diastereomer type A) (0.28 g, 0.86 mmol) was dissolved in N,N-dimethylacetamide dimethyl acetal (1 mL) and the solution was stirred for one hour at 110° C. The mixture was concentrated and then the residue was dissolved in 1,4-dioxane (2 mL). To the solution was added 1N sodium hydroxide aqueous solution (1 mL), hydroxylamine hydrochloride (0.06 g, 0.86 mmol) and acetic acid (2 mL) and the mixture was refluxed for one hour. After cooling to room temperature, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic extracts were dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by flash column chromatography on silica gel (hexane/ethyl acetate=5/1 to 1/1 as eluants) to yield 7-[4-(3-methyl-[1,2,4]oxadiazol-5-yl)-phenyl]-4-((R)-1-phenyl-ethyl)-[1,4]oxazepane (diastereomer type A) (0.27 g, 0.75 mmol, 88%) as white solid.

Workup

  1. concentrationThe mixture was concentrated
  2. dissolutionthe residue was dissolved in 1,4-dioxane (2 mL)
  3. temperaturethe mixture was refluxed for one hour
  4. temperatureAfter cooling to room temperature
  5. extractionextracted with ethyl acetate
  6. dry with materialThe organic extracts were dried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting residue was purified by flash column chromatography on silica gel (hexane/ethyl acetate=5/1 to 1/1 as eluants)

Sources & evidence

ORD record
ord-1c754b339f3243629fb03fa7d096cfd5
Source dataset
uspto-grants-2015_08
Patent number
US09108957B2

Reaction notes

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