Methanol → 3-tert-Butoxycarbonyl-7-chloro-6-(1-cyano-ethylthio)-2,3,4,5-tetrahydro-1H-benzo[d]azepine

HRID 911749ノート

反応式

HRID 911749 の反応式
[OH-].[K+].[C:3]([O:7][C:8]([N:10]1[CH2:16][CH2:15][C:14]2[C:17]([S:22][C:23](=O)N(C)C)=[C:18]([Cl:21])[CH:19]=[CH:20][C:13]=2[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].[H-].[Na+].BrC(C)[C:32]#[N:33].[CH3:35]O>CCOC(C)=O>[C:3]([O:7][C:8]([N:10]1[CH2:16][CH2:15][C:14]2[C:17]([S:22][CH:23]([C:32]#[N:33])[CH3:35])=[C:18]([Cl:21])[CH:19]=[CH:20][C:13]=2[CH2:12][CH2:11]1)=[O:9])([CH3:4])([CH3:5])[CH3:6]

参加物

7

反応物 5

HCID 887MethanolHCID 14797Potassium HydroxideHCID 24758Sodium hydrideHCID 1405382-BromopropionitrileHCID 576559793-tert-butoxycarbonyl-7-chloro-6-dimethylaminocarbonylthio-2,3,4,5-tetrahydro-1H-benzo[d]azepine

生成物 1

HCID 667072883-tert-Butoxycarbonyl-7-chloro-6-(1-cyano-ethylthio)-2,3,4,5-tetrahydro-1H-benzo[d]azepine収率 89%

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

反応条件

温度
80 °C

実験手順

Add potassium hydroxide (10.8 g, 192 mmol) to a solution of 3-tert-butoxycarbonyl-7-chloro-6-dimethylcarbamoylthio-2,3,4,5-tetrahydro-1H-benzo[d]azepine (3 g, 7.8 mmol) in degassed methanol (150 mL) under a nitrogen atmosphere. Heat the mixture at 80° C. for 6 h. Cool the mixture to ambient temperature, then concentrate in vacuo to an oil. Dissolve the oil in EtOAc (50 mL), wash with aqueous saturated ammonium chloride (30 mL). Separate the organic layer and extract the aqueous layer with EtOAc (3×50 mL). Dry the combined organic extracts over Na2SO4, filter and concentrate in vacuo to an oil (2.4 g). Dissolve the oil in anhydrous DMF (50 mL). Slowly add sodium hydride (470 mg, 11.7 mmol) portionwise over 5 min followed by 2-bromopropionitrile (1 mL, 11.7 mmol). Stir the mixture under nitrogen at ambient temperature for 16 h. Dilute the mixture slowly with EtOAc (100 mL) and wash with cold aqueous saturated ammonium chloride (50 mL). Separate the organic layer and extract the aqueous-layer with EtOAc (3×50 mL). Combine the organic extracts and concentrate in vacuo. Purify the crude mixture by chromatography on silica gel eluting with hexane/EtOAc (19:1 to 3:1 gradient) to obtain the desired intermediate (2.5 g, 89%). MS (ES+) m/z: 267.2 (M-Boc)+.

後処理

  1. temperatureCool the mixture to ambient temperature
  2. concentrationconcentrate in vacuo to an oil
  3. dissolutionDissolve the oil in EtOAc (50 mL)
  4. washwash with aqueous saturated ammonium chloride (30 mL)
  5. customSeparate the organic layer
  6. extractionextract the aqueous layer with EtOAc (3×50 mL)
  7. dry with materialDry the combined organic extracts over Na2SO4
  8. filtrationfilter
  9. concentrationconcentrate in vacuo to an oil (2.4 g)
  10. dissolutionDissolve the oil in anhydrous DMF (50 mL)
  11. washwash with cold aqueous saturated ammonium chloride (50 mL)
  12. customSeparate the organic layer
  13. extractionextract the aqueous-layer with EtOAc (3×50 mL)
  14. concentrationCombine the organic extracts and concentrate in vacuo
  15. customPurify the crude mixture by chromatography on silica gel eluting with hexane/EtOAc (19:1 to 3:1 gradient)

出典と根拠

ORDレコード
ord-eff8b36f4f564fa5be74ab1532ce8f1b
出典データセット
uspto-grants-2011_09
特許番号
US08022062B2

反応ノート

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