Sulfuric Acid → 2-(3-(3,4-Dichlorophenyl)pyrrolidin-3-yl)ethanol

HRID 323199Notes

Reaction equation

HRID 323199 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].S(=O)(=O)(O)O.S(=O)(=O)(O)O.C1COCC1.C([O:24][C:25](=O)[CH2:26][C:27]1([C:33]2[CH:38]=[CH:37][C:36]([Cl:39])=[C:35]([Cl:40])[CH:34]=2)[CH2:31][C:30](=O)[NH:29][CH2:28]1)C>C1COCC1.ClCCl.C(OCC)(=O)C.CCCCCC>[Cl:40][C:35]1[CH:34]=[C:33]([C:27]2([CH2:26][CH2:25][OH:24])[CH2:31][CH2:30][NH:29][CH2:28]2)[CH:38]=[CH:37][C:36]=1[Cl:39]

Participants

8

Reactant 4

HCID 1118Sulfuric Acid2×HCID 21226445Aluminium lithium hydride2×HCID 54080079(3-(3,4-Dichlorophenyl)-5-oxopyrrolidin-3-yl)acetic acid ethyl esterHCID 68124251Sulfuric acid tetrahydrofuran

Product 1

HCID 184644272-(3-(3,4-Dichlorophenyl)pyrrolidin-3-yl)ethanol

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent3×HCID 21226206Ethyl acetate hexaneSolvent

Procedure

Cool a solution of lithium aluminum hydride (450 mL, 1M in THF, 450 mmol) to −10° C. in a ice/acetone bath. Add dropwise, a solution of sulfuric acid (12 mL, 99.999%, 225.3 mmol) in THF (35 mL). (Use caution when adding the sulfuric acid to the THF and also when adding the sulfuric acid/THF solution to the lithium aluminum hydride solution). After the addition is complete, stir for 1 hour. Warm to ambient temperature and stir for 2 hours. Add dropwise, a solution of (3-(3,4-dichlorophenyl)-5-oxopyrrolidin-3-yl)acetic acid ethyl ester (23.2 g, 73.4 mmol) in THF (70 mL). Heat to 45-50° C. for 36 hours. Cool in an ice bath. Add dropwise, a solution of THF/water (1/1, 70 mL). Filter and rinse the filter cake with THF and dichloromethane, retain the filtrate. Combine the filter cake with THF/water/15% sodium hydroxide solution (1 L/70 mL/20 mL) and vigorously stir for 2 hours. Filter and combine the filtrate with the filtrate obtained above. Concentrate the combined filtrates in vacuo to obtain a residue. Dissolve the residue in dichloromethane and dry over MgSO4, filter, and concentrate in vacuo to obtain a residue. Recrystallize the residue from diethyl ether to give the title compound: Rf=0.27 (silica gel, 9:1:0.2; dichloromethane/methanol/ammonium hydroxide); mp; 91-94° C. Elemental Analysis calculated for C12H15Cl2NO: C 55.40; H 5.81; N 5.38; Found: C 55.64; H 5.88; N 5.20.

Workup

  1. additionAdd dropwise
  2. additionAfter the addition
  3. stirringstir for 2 hours
  4. additionAdd dropwise
  5. temperatureHeat to 45-50° C. for 36 hours
  6. temperatureCool in an ice bath
  7. additionAdd dropwise
  8. filtrationFilter
  9. washrinse the filter cake with THF and dichloromethane
  10. stirringvigorously stir for 2 hours
  11. filtrationFilter
  12. customobtained above
  13. concentrationConcentrate the combined filtrates in vacuo
  14. customto obtain a residue
  15. dry with materialdry over MgSO4
  16. filtrationfilter
  17. concentrationconcentrate in vacuo
  18. customto obtain a residue
  19. customRecrystallize the residue from diethyl ether

Sources & evidence

ORD record
ord-ef935487d2ca4ba1ad3ad65b8147a5e4
Source dataset
uspto-grants-2001_04
Patent number
US06211199B1

Reaction notes

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