Methanol → Galantamine, (+)-

HRID 22462

Reaction equation

HRID 22462 reaction equation
CCC(C)[BH-](C(C)CC)C(C)CC.[Li+].[CH3:15][N:16]1[CH2:33][C:31]2=[C:32]3[C:27](=[C:28]([O:34][CH3:35])[CH:29]=[CH:30]2)[O:26][C@H:25]2[C@@:19]3([CH:20]=[CH:21][C:22]([CH2:24]2)=[O:23])[CH2:18][CH2:17]1.CO>C1COCC1.C(Cl)(Cl)Cl>[CH3:15][N:16]1[CH2:33][C:31]2=[C:32]3[C:27](=[C:28]([O:34][CH3:35])[CH:29]=[CH:30]2)[O:26][C@H:25]2[C@@:19]3([CH:20]=[CH:21][C@@H:22]([OH:23])[CH2:24]2)[CH2:18][CH2:17]1

Participants

6

Reactant 3

HCID 887MethanolHCID 441596(+)-NarwedineHCID 3611392Lithium tri-s-butylborohydride2×

Product 1

HCID 906210Galantamine, (+)-

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

2 mmole (1N in tetrahydrofuran {THF}) of L-Selectride® (lithium tri-sec-butylborohydride, Aldrich) is charged into 8 ml THF and cooled to -78° C. 1 mmole of (+)-narwedine in 50 ml THF is added dropwise over a period of 30 minutes. After addition, the solution is stirred at -78° C. for 2 hours and then warmed to 0° C. 0.4 ml of methanol is added and the solution is warmed to 25° C. and stirred for 15 minutes. Solvent is then evaporated under vacuum to dryness to obtain a syrup. The syrup is dissolved in 0.5 ml CHCl3 and the solution is loaded into a SiO2 200-400 mesh, 6A, column. The column is eluted with a solvent mixture of CH2Cl2 /CH3OH 6:1 to obtain pure (+)-galanthamine.

Workup

  1. additionAfter addition
  2. temperaturewarmed to 0° C
  3. temperaturethe solution is warmed to 25° C.
  4. stirringstirred for 15 minutes
  5. customSolvent is then evaporated under vacuum to dryness
  6. customto obtain a syrup
  7. washThe column is eluted with a solvent mixture of CH2Cl2 /CH3OH 6:1

Sources & evidence

ORD record
ord-776d92d9740843baac2ed5cc2f7eae00
Source dataset
uspto-grants-1995_06
Patent number
US05428159

Linked notes

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