Tetrahydrofuran → 2-(3-Phenylpyrrolidin-3-yl)ethanol

HRID 343515Notes

Reaction equation

HRID 343515 reaction equation
C([O:3][C:4](=O)[CH2:5][C:6]1([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:10][C:9](=O)[NH:8][CH2:7]1)C.O1CCCC1.[H-].[Al+3].[Li+].[H-].[H-].[H-].C(OCC)(=O)C.CCCCCC>ClCCl>[C:12]1([C:6]2([CH2:5][CH2:4][OH:3])[CH2:10][CH2:9][NH:8][CH2:7]2)[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

6

Reactant 4

HCID 8028Tetrahydrofuran3×HCID 21226206Ethyl acetate hexaneHCID 21226445Aluminium lithium hydrideHCID 53754019HCID 53754019, compound

Product 1

HCID 184645642-(3-Phenylpyrrolidin-3-yl)ethanol

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
5 °C

Procedure

Combine (3-phenyl-5-oxopyrrolidin-3-yl)acetic acid ethyl ester (301 g, 1.25 mol) and tetrahydrofuran (3.5 L). Cool to about 5° C. Slowly, add portionwise over about 45 minutes a solution of lithium aluminum hydride in tetrahydrofuran (3.9 L, 1M, 3.9 mol). After the addition is complete heat to 60° C. After 18 hours, cool in an ice-bath. Add water/tetrahydrofuran 1/1 (1.95 L) dropwise at such a rate that the temperature of the reaction mixture does not rise above 20° C. Dilute the reaction mixtur tetrahydrofura tetrahydrofuran (2.25 L) and stir. After 1.5 hours, filter the reaction mixture. Suspend the solids in diethyl ether (3 L) and filter. Combine the filtrates and concentrate the in vacuo to give a residue. Combine the residue and dichloromethane (4 L) and extract three times with water (1 L). Dry the organic layer over MgSO4, filter, and concentrate in vacuo to obtain a solid. Triturate the solid with diethyl ether (0.3 L), collect by filtration, rinse with diethyl ether, and dry to give the title compound: Rf =0.12 (silica gel dichloromethane/methanol/concentrated aqueous ammonia, 9/1/0.1).

Workup

  1. additionAfter the addition
  2. temperatureis complete heat to 60° C
  3. temperaturecool in an ice-bath
  4. customdoes not rise above 20° C
  5. waitAfter 1.5 hours
  6. filtrationfilter the reaction mixture
  7. filtrationfilter
  8. concentrationconcentrate the in vacuo
  9. customto give a residue
  10. extractionextract three times with water (1 L)
  11. dry with materialDry the organic layer over MgSO4
  12. filtrationfilter
  13. concentrationconcentrate in vacuo
  14. customto obtain a solid
  15. customTriturate the solid with diethyl ether (0.3 L)
  16. filtrationcollect by filtration
  17. washrinse with diethyl ether
  18. customdry

Sources & evidence

ORD record
ord-d2421666db7343ae8e1921e67128128a
Source dataset
uspto-grants-1999_01
Patent number
US05861417

Reaction notes

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