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

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)+.

1. extractionThe di-aldehyde was extracted with DCE (2×15 mL)
2. washwashed with water (5×10 mL
3. customuntil no reaction to starch iodide
4. washaqueous wash),
5. customThe solvent was removed in vacuo
6. customthe residue was quenched with saturated aqueous NaHCO3 solution
7. extractionThe product was extracted with EtOAc (3×30 mL)
8. washwashed with saturated aqueous NaCl solution (1×30 mL)
9. dry with materialdried over Na2SO4
10. filtrationfiltered through a silica pad (2×3 in)
11. washeluted with 100% EtOAc
12. concentrationconcentrated

ORD record

ord-b0a43e8d8ef34da0b1026e8a6c36f9e3

Source dataset

uspto-grants-2007_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07241887B2