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

HRID 323253Notes

Reaction equation

HRID 323253 reaction equation
[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]

Participants

6

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-10 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-6bffba62f0374b65b5423a79f7662d90
Source dataset
uspto-grants-2001_04
Patent number
US06211199B1

Reaction notes

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