Water → 3-Benzyl-8,8-dimethoxy-3-aza-bicyclo[3.2.1]oct-6-ene

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Reaction Conditions

Reaction Steps

To a 3 L 3NRB equipped with a thermometer, addition funnel and water condenser was added dioxane (1000 mL) then sodium (44.7 g, 1.94 mol). Upon heating under reflux (T ˜100° C.), the sodium became a dispersed immiscible liquid. While maintaining this gentle reflux, a solution of 3-benzyl-1,5,6,7-tetrachloro-8,8-dimethoxy-3-aza-bicyclo[3.2.1]oct-6-ene (52.5 g, 0.132 mol), t-butanol (160 mL, 1.67 mol) and dioxane (150 mL) was added dropwise via the addition funnel over 30 min and heat continued overnight. Upon cooling to 70° C., the residual unreacted sodium was quenched with MeOH (150 mL) then water (1 L). The dioxane and MeOH were then removed in vacuo. The product was extracted from the aqueous layer with EtOAc (3×300 mL), washed with saturated aqueous NaCl solution (1×300 mL), dried over Na2SO4, filtered and concentrated to yield a dark brown oil (29.2 g, 85%). (TLC 40% EtOAc/hexanes Rf 0.35); 1H NMR (400 MHz, CDCl3) δ 7.28–7.20 (5H), 6.01 (t, J=1.6 Hz, 2H), 3.65 (s, 2H), 3.23 (s, 3H), 3.17 (s, 3H), 2.63 (s, 2H), 2.57 (AB d, J=10.1 Hz, 2H), 2.44 (AB d, J=10.1 Hz, 2H); GCMS m/z 259 (M)+; APCI MS m/z 260.2 (M+1)+.

Provenance & Evidence