Sulfuric Acid → 2-[3-(3,4-Dichlorophenyl)piperidin-3-yl]ethanol

HRID 323253ノート

反応式

HRID 323253 の反応式
[H-].[Al+3].[Li+].[H-].[H-].[H-].S(=O)(=O)(O)O.[Cl:12][C:13]1[CH:14]=[C:15]([C:20]2([CH2:27][CH2:28][O:29][Si](C(C)(C)C)(C)C)[CH2:25][CH2:24][C:23](=O)[NH:22][CH2:21]2)[CH:16]=[CH:17][C:18]=1[Cl:19].O1CCCC1.O>O1CCCC1>[Cl:12][C:13]1[CH:14]=[C:15]([C:20]2([CH2:27][CH2:28][OH:29])[CH2:25][CH2:24][CH2:23][NH:22][CH2:21]2)[CH:16]=[CH:17][C:18]=1[Cl:19]

参加物

6

反応物 4

HCID 1118Sulfuric AcidHCID 184647403-(3,4-Dichlorophenyl)-3-(2-(t-butyldimethylsilyloxy)ethyl)-6-oxopiperidineHCID 21226445Aluminium lithium hydrideHCID 21881883Oxolane--water (1/1)

生成物 1

HCID 154604002-[3-(3,4-Dichlorophenyl)piperidin-3-yl]ethanol

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-10 °C

実験手順

Combine a solution of lithium aluminum hydride (42 mL, 1 M in THF, 42.0 mmol). Cool to about −10° C. using an isopropyl alcohol/ice bath. Slowly add a solution of sulfuric acid (1.15 mL, 21.6 mmol) in tetrahydrofuran (4 mL) at such a rate that the reaction temperature does not rise above −10° C. Stir vigorously and warm to ambient temperature. After 2 hours, add a solution of 3-(3,4-dichlorophenyl)-3-(2-(t-butyldimethylsilyloxy)ethyl)-6-oxopiperidine (5.56 g, 13.85 mmol) in tetrahydrofuran (12 mL). Heat to reflux. After 18 hours, add 1/1 tetrahydrofuran/water. After 1 hour, filter and rinse with dichloromethane. Suspend the solids removed by filtration in tetrahydrofuran (400 mL). To the tetrahydrofuran suspension add water (20 mL) and 15% aqueous sodium hydroxide solution (8 mL) and stir vigorously. After 2 hours, filter. Combine the filtrates and concentrate in vacuo to give an aqueous suspension. Extract twice with dichloromethane. Dry the organic layers over Na2SO4, filter, and concentrate in vacuo to give the title compound.

後処理

  1. customdoes not rise above −10° C
  2. temperaturewarm to ambient temperature
  3. temperatureHeat to reflux
  4. waitAfter 18 hours
  5. waitAfter 1 hour
  6. filtrationfilter
  7. washrinse with dichloromethane
  8. customremoved by filtration in tetrahydrofuran (400 mL)
  9. additionTo the tetrahydrofuran suspension add water (20 mL) and 15% aqueous sodium hydroxide solution (8 mL)
  10. stirringstir vigorously
  11. waitAfter 2 hours
  12. filtrationfilter
  13. concentrationconcentrate in vacuo
  14. customto give an aqueous suspension
  15. extractionExtract twice with dichloromethane
  16. dry with materialDry the organic layers over Na2SO4
  17. filtrationfilter
  18. concentrationconcentrate in vacuo

出典と根拠

ORDレコード
ord-6bffba62f0374b65b5423a79f7662d90
出典データセット
uspto-grants-2001_04
特許番号
US06211199B1

反応ノート

読み込み中…