Methanol → (-)-Galantamine

HRID 22463

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

Conditions

Temperature: -78 °C

Procedure

2 mmole (1 N 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 286 mg of pure (-)-galanthamine (a yield of 99.5%). HPLC of the resultant mixture indicates there is no epigalanthamine or lycoramine present. {m.p. 128°-129° C.; [α]D25 =-93.4}. Natural (-)-galanthamine has a melting point of 126°-127° C. ([α]D25 =-91.0)

Workup

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

Sources & evidence

ORD record: ord-6c34087f4ae24460afa564bb7fcb8465
Source dataset: uspto-grants-1995_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05428159

Linked notes

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