(3R,11bR)-1,3,4,6,7,11b-Hexahydro-9,10-dimethoxy-3-(2-methylpropyl)-2H-benzo(a)quinolizin-2-one → alpha-Dihydrotetrabenazine

Participants

Reaction Conditions

Reaction Steps

(3R,11bR)-Tetrabenazine 1c.1 (2 g, 6.3 mmol) was dissolved in EtOH (70 mL) and cooled to 0° C. Sodium borohydride (261 mg, 6.9 mmol) was then added in portions at 0° C. The reaction was complete after 30 minutes and quenched with saturated NH4Cl (4 mL). The white precipitate formed was filtered and washed with EtOH (5 mL, 2×). The EtOH was removed in vacuo and the aqueous layer extracted 3× with CH2Cl2 (50 mL). The organic layers were combined, dried over MgSO4 and concentrated. The crude product was purified via flash column chromatography (0.5:9.5 MeOH:CH2Cl2) to give 1.6 g (5 mmol) of (2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol ((2R,3R,11bR)-dihydrotetrabenazine) 1d.1 and 410 mg (1.3 mmol) of (2S,3R,11bR)-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol ((2S,3R,1bR)-dihydrotetrabenazine) 1d.2. (2R,3R,11bR)-Dihydrotetrabenazine 1d.1: MS calcd: (319); Found 320.3 (M+H). (2S,3R,11bR)-Dihydrotetrabenazine 1d.2: MS calcd: (319); Found 320.3 (M+H).

Provenance & Evidence