Hexane → N-Methyl-6-amino-4a-(3-methoxyphenyl)-8a-methyloctahydroisoquinoline

Participants

Reaction Conditions

Reaction Steps

A slurry of oxime 19 (2.35 g, 0.077 mol) in anhydrous isopropanol (100 mL) and anhydrous toluene (200 mL) was heated to reflux until the solution became clear. The heat was turned off, and Na (20 g, 0.87 mol) was added carefully in a such rate that a steady reflux was maintained (make 30-40 pieces and store under hexane) over 1.5 h. The first addition was kept small. (Note hydrogen evolution!). At the end the reaction was slower, so the heating mantle was turned back on to speed things up. The reaction mixture was heated to reflux until all Na was consumed followed by cooling to 50° C. and quenching with careful addition of water (250 mL). The toluene layer was separated and the aqueous layer extracted with EtOAc (3×100 mL). The combined organic layers were dried (MgSO4), filtered, and concentrated under reduced pressure yielding crude product. The crude product was purified by flash chromatography (50% CMA80 in CHCl3) to afford 2.11 g (94%) of 20 as a colorless oil: LCMS (APCI): m/z 289.4 (M+H)+; 1H NMR (CDCl3, 300 MHz) δ 7.14-7.44 [m, 3H], 6.71-6.74 [m, 1H], 3.80 [s, 3H], 3.05 [m, 1H], 2.77 [m, 1H], 2.64 [d, J=12 Hz, 1H], 2.27-2.30 [m, 2H], 2.26 [s, 3H], 2.02-2.12 [m, 3H], 1.68-1.71 [m, 2H], 1.46-1.49 [m, 2H], 1.24 [m, 3H], 1.20 [s, 3H]; 13C NMR (CDCl3, 300 MHz) δ 159.2, 150.2, 128.5, 121.8, 116.5, 110.0, 65.4, 55.5, 53.0, 47.1, 46.7, 43.8, 43.3, 36.6, 36.2, 32.2, 25.8.

Provenance & Evidence