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

HRID 515484ノート

反応式

HRID 515484 の反応式
[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

参加物

7

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 878351,1-Dimethoxyethyl(dimethyl)amine溶媒

反応条件

温度
110 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-1c754b339f3243629fb03fa7d096cfd5
出典データセット
uspto-grants-2015_08
特許番号
US09108957B2

反応ノート

読み込み中…