Methylephedrine → (-)-Galantamine

HRID 850694

반응식

HRID 850694 반응식
[H-].[Al+3].[Li+].[H-].[H-].[H-].C[C@H](N(C)C)[C@H](O)C1C=CC=CC=1.C(N1C=CC=CC1N)C.[CH3:29][N:30]1[CH2:49][C:43]2[CH:44]=[CH:45][C:46]([O:47][CH3:48])=[C:41]3[C:42]=2[C@:33]2([C@@H:39]([O:40]3)[CH2:38][C:36](=[O:37])[CH:35]=[CH:34]2)[CH2:32][CH2:31]1>CCOCC>[CH3:29][N:30]1[CH2:49][C:43]2=[C:42]3[C:41](=[C:46]([O:47][CH3:48])[CH:45]=[CH:44]2)[O:40][C@@H:39]2[C@:33]3([CH:34]=[CH:35][C@H:36]([OH:37])[CH2:38]2)[CH2:32][CH2:31]1

참가 물질

6

반응물 4

HCID 64782MethylephedrineHCID 10356588NarwedineHCID 19364846n-Ethyl-2-aminopyridineHCID 21226445Aluminium lithium hydride

생성물 1

HCID 9651(-)-Galantamine수율 36%

시약·촉매·용매 1

HCID 3283Diethyl Ether용매2회

실험 절차

Lithium aluminium hydride (1M in ether, 1.2 ml, 1.20 mmol) was placed in a two necked round bottom flask fitted with a reflux condenser and nitrogen inlet. (-)-N-methylephedrine (0.23 g, 1.26 mmol) in ether (1 ml) was added dropwise and the solution was heated at reflux for 1 hour then cooled to room temperature. N-Ethyl-2-amino-pyridine (0.31 g, 2.52 mmol) in ether (1 ml) was added and the bright yellow solution was heated under reflux for a further 1 hour. The solution was cooled to -78° C. and solid racemic narwedine (0.10 g, 0.35 mmol) was added. The suspension was stirred for 3 hours at -78° C. and then allowed to warm to room temperature over 1 hour. The reaction was quenched with hydrochloric acid (3M, 2 ml). The aqueous layer was removed and basified with KOH to pH 14. The remaining mixture was extracted with dichloromethane (3×10 ml) and the combined organic layers were washed with water (5 ml) and brine (5 ml) and dried over magnesium sulphate. Filtration and evaporation gave an orange oil which was flash chromatographed on silica in dichloromethane-methanol 10:1 to yield (-)-galanthamine (50% e.e.) as a white solid (0.036 g, 36%), pure by NMR.

후처리

  1. customfitted with a reflux condenser and nitrogen inlet
  2. temperaturethe solution was heated
  3. temperatureat reflux for 1 hour
  4. temperaturethe bright yellow solution was heated
  5. temperatureunder reflux for a further 1 hour
  6. temperatureThe solution was cooled to -78° C.
  7. temperatureto warm to room temperature over 1 hour
  8. customThe reaction was quenched with hydrochloric acid (3M, 2 ml)
  9. customThe aqueous layer was removed
  10. extractionThe remaining mixture was extracted with dichloromethane (3×10 ml)
  11. washthe combined organic layers were washed with water (5 ml) and brine (5 ml)
  12. dry with materialdried over magnesium sulphate
  13. filtrationFiltration and evaporation
  14. customgave an orange oil which
  15. customchromatographed on silica in dichloromethane-methanol 10:1

출처 및 근거

ORD 기록
ord-a7e53ec75ed941a58c862f1e794ab4d2
출처 데이터셋
uspto-grants-2000_01
특허 번호
US06018043

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