4-Methoxybenzylamine → 1,5,6,7-Tetrachloro-8,8-dimethoxy-3-(4-methoxy-benzyl)-3-aza-bicyclo[3.2.1]oct-6-ene

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Reaction Steps

1,4,5,6-Tetrachloro-7,7-dimethoxy-bicyclo[2.2.1]hept-5-ene-2,3-diol (1.23 g, 3.80 mmol) and sodium periodate (1.19 g, 3.80 mmol) were stirred vigorously for 1.5 h in DCE (10 mL) and water (10 mL). The di-aldehyde was extracted with DCE (2×15 mL), washed with water (5×10 mL, or until no reaction to starch iodide is observed in the aqueous wash), then filtered through a cotton plug under N2 into a slurry of p-methoxybenzylamine (0.52 mL, 3.99 mmol) and NaBH(OAc)3 (2.58 g, 12.16 mmol) in DCE (10 mL). After 3 h at room temperature the reaction was judged complete by TLC. The solvent was removed in vacuo, and the residue was quenched with saturated aqueous NaHCO3 solution. The product was extracted with EtOAc (3×30 mL), washed with saturated aqueous NaCl solution (1×30 mL), dried over Na2SO4, filtered through a silica pad (2×3 in), eluted with 100% EtOAc and concentrated to yield the title compound as a white solid (1.32 g, 82%). (TLC 30% EtOAc/hexanes Rf 0.65); 1H NMR (400 MHz, CDCl3) δ 7.12 (d, J=8.3 Hz, 2H), 6.81 (d, J=8.3 Hz, 2H), 3.77 (s, 3H), 3.61 (s, 2H), 3.59 (s, 3H), 3.56 (s, 3H), 2.76 (d, J=11.4 Hz, 2H), 2.71 (d, J=11.1 Hz, 2H); GCMS m/z 427 (M)+.

Provenance & Evidence