Tetrahydrofuran → Eletriptan

HRID 473059Notes

Reaction equation

HRID 473059 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].C1COCC1.[CH3:12][N:13]1[CH2:17][CH2:16][CH2:15][C@@H:14]1[C:18]([C:20]1[C:28]2[C:23](=[CH:24][CH:25]=[C:26]([CH2:29][CH2:30][S:31]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)(=[O:33])=[O:32])[CH:27]=2)[NH:22][CH:21]=1)=O.[OH-].[Na+]>O>[CH3:12][N:13]1[CH2:17][CH2:16][CH2:15][C@@H:14]1[CH2:18][C:20]1[C:28]2[C:23](=[CH:24][CH:25]=[C:26]([CH2:29][CH2:30][S:31]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)(=[O:32])=[O:33])[CH:27]=2)[NH:22][CH:21]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 9908745(R)-(1-methylpyrrolidin-2-yl)(5-(2-(phenylsulfonyl)ethyl)-1H-indol-3-yl)methanoneHCID 21226445Aluminium lithium hydride

Product 1

HCID 77993EletriptanYield 75%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
2.5 °C

Procedure

To a suspension of LAH and THF was slowly charged (R)-(1-methylpyrrolidin-2-yl)(5-(2-(phenylsulfonyl)ethyl)-1H-indol-3-yl)methanone at 0° C. and then the reaction was slowly heated to reflux. Upon completion of the reaction in about 3-5 h, the reaction was cooled to 0-5° C. and 1N NaOH soln and H2O were sequentially charged. The solids were filtered and the precipitate washed with additional THF. The filtrate was distilled to dryness under reduced pressure. The residue was dissolved in water and the aqueous layer extracted with dichloromethane and dried over sodium sulfate and distilled to give the title compound in 75-80% yield.

Workup

  1. customat 0° C.
  2. temperaturethe reaction was slowly heated to reflux
  3. customUpon completion of the reaction in about 3-5 h
  4. filtrationThe solids were filtered
  5. washthe precipitate washed with additional THF
  6. distillationThe filtrate was distilled to dryness under reduced pressure
  7. dissolutionThe residue was dissolved in water
  8. extractionthe aqueous layer extracted with dichloromethane
  9. dry with materialdried over sodium sulfate
  10. distillationdistilled

Sources & evidence

ORD record
ord-0fca0fefa34d444a9f9b39b509f73dd4
Source dataset
uspto-grants-2014_01
Patent number
US08633239B2

Reaction notes

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