Ethyl Acetate → 1-tosyl-2-(S)-pyrrolidinemethanol

HRID 1976237Notes

Reaction equation

HRID 1976237 reaction equation
[S:1]([N:11]1[CH2:18][CH2:17][CH2:16][C@H:12]1[C:13](O)=[O:14])([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:3])=[O:2].[H-].[Al+3].[Li+].[H-].[H-].[H-].C(OCC)(=O)C>CCOCC>[S:1]([N:11]1[CH2:18][CH2:17][CH2:16][C@H:12]1[CH2:13][OH:14])([C:4]1[CH:5]=[CH:6][C:7]([CH3:8])=[CH:9][CH:10]=1)(=[O:2])=[O:3]

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 691957(2S)-1-(4-methylbenzenesulfonyl)pyrrolidine-2-carboxylic acidHCID 21226445Aluminium lithium hydride

Product 1

HCID 7244141-tosyl-2-(S)-pyrrolidinemethanolYield 53.1%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

A solution of 1-tosyl-L-proline (17.8 g) prepared in Reference Example 38 in anhydrous ether (80 ml) was dropwise added to a suspension of lithium aluminum hydride (3.76 g) in anhydrous ether (80 ml) over 30 minutes with ice-cooling. After stirring the reaction liquid at room temperature for one hour, 100 ml of ethyl acetate was added thereto and the resulting mixture was stirred for additional 16 hours. The insolubles formed was filtered off through a Celite layer, the organic phase obtained was washed with water and dried over anhydrous magnesium sulfate. The organic phase was concentrated, then the resulting residue was subjected to silica gel column chromatography and eluted with chloroform/ethyl acetate (98/2) to give 8.96 g (yield 53.1%) of the title compound.

Workup

  1. temperaturecooling
  2. customthe reaction liquid at room temperature for one hour
  3. stirringthe resulting mixture was stirred for additional 16 hours
  4. customThe insolubles formed
  5. filtrationwas filtered off through a Celite layer
  6. customthe organic phase obtained
  7. washwas washed with water
  8. dry with materialdried over anhydrous magnesium sulfate
  9. concentrationThe organic phase was concentrated
  10. washeluted with chloroform/ethyl acetate (98/2)

Sources & evidence

ORD record
ord-d1ef709fcc49475c8a7262c20ad85721
Source dataset
uspto-grants-2001_05
Patent number
US06225306B1

Reaction notes

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