Sodium Hydroxide → (2R,8aS)-2-methoxy-1,2,3,5,6,7,8,8a-octahydroindolizin-7-one

HRID 1245025Notes

Reaction equation

HRID 1245025 reaction equation
N1CCCC1.C(OC([N:16]1[CH2:20][C@H:19]([O:21][CH3:22])[CH2:18][C@H:17]1[CH2:23][C:24](=[O:31])[CH2:25][C:26](OCC)=O)=O)C1C=CC=CC=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].[OH-].[Na+]>C(OCC)(=O)C.[OH-].[OH-].[Pd+2].C(O)C.O1CCCC1>[CH3:22][O:21][C@H:19]1[CH2:20][N:16]2[C@H:17]([CH2:23][C:24](=[O:31])[CH2:25][CH2:26]2)[CH2:18]1

Participants

9

Reactant 4

HCID 14798Sodium HydroxideHCID 31268PyrrolidineHCID 21226445Aluminium lithium hydrideHCID 57501855(2S,4R)-1-Benzyloxycarbonyl-2-(3-ethoxycarbonyl-2-oxopropyl)-4-methoxypyrrolidine

Product 1

HCID 57457952(2R,8aS)-2-methoxy-1,2,3,5,6,7,8,8a-octahydroindolizin-7-oneYield 59.1%

Reagents, catalysts & solvents 4

HCID 9942167Palladium hydroxideCatalystHCID 702EthanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

3.79 ml (45.4 mmol) of pyrrolidine, 1.50 g of molecular sieves (MS4A) and 3.75 g of 20% palladium hydroxide on carbon were added to a solution of 15.00 g (41.3 mmol) of (2S,4R)-1-benzyloxycarbonyl-2-(3-ethoxycarbonyl-2-oxopropyl)-4-methoxypyrrolidine [prepared as described in Preparative Example 1 (ii)′ above] in 150 ml of ethyl acetate and the mixture was then stirred for 2 hours at room temperature under a hydrogen atmosphere. At the end of this time, the reaction mixture was filtered and the filtrate was concentrated by evaporation under reduced pressure. The resulting residue was dissolved in 150 ml of tetrahydrofuran, and the solution thus obtained was added dropwise with stirring to an ice-cooled suspension of 4.70 g (124 mmol) of lithium aluminum hydride in 100 m] of tetrahydrofuran, and the reaction mixture was then stirred for a further 18 hours at room temperature. At the end of this time, 19 ml of a 4% aqueous solution of sodium hydroxide were added carefully to the reaction mixture at 0° C., and after the addition of 250 ml of ethanol, the resulting mixture was filtered. The filtrate thus obtained was concentrated by evaporation under reduced pressure and the residue was purified by chromatography on an alumina column using ethyl acetate as the eluant to afford 4.13 g (yield: 59%) of the title compound as a pale brown powder.

Workup

  1. customprepared
  2. filtrationAt the end of this time, the reaction mixture was filtered
  3. concentrationthe filtrate was concentrated by evaporation under reduced pressure
  4. dissolutionThe resulting residue was dissolved in 150 ml of tetrahydrofuran
  5. customthe solution thus obtained
  6. additionwas added dropwise
  7. temperaturecooled
  8. stirringthe reaction mixture was then stirred for a further 18 hours at room temperature
  9. filtrationthe resulting mixture was filtered
  10. customThe filtrate thus obtained
  11. concentrationwas concentrated by evaporation under reduced pressure
  12. customthe residue was purified by chromatography on an alumina column

Sources & evidence

ORD record
ord-a0ddee4167b94c6da33cd0b97ae89848
Source dataset
uspto-grants-2006_10
Patent number
US07122666B2

Reaction notes

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