2,3,5,6-tetrahydro-1H-1,5-benzodiazocin-4-one

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A Schlenk tube was charged with CuI (9.6 mg, 0.050 mmol, 5.0 mol %), 2-azetidinone (86 mg, 1.21 mmol), K3PO4 (430 mg, 2.03 mmol), evacuated, and backfilled with Ar. N,N′-Dimethylethylenediamine (11 μL, 0.103 mmol, 10 mol %), 2-iodobenzylamine (132 μL, 1.00 mmol), and toluene (1 mL) were added under Ar. The Schlenk tube was sealed and the reaction mixture was stirred at 100° C. for 22 h. The resulting suspension was allowed to reach room temperature, poured into a solution of 30% aq ammonia (1 mL) in water (20 mL), and extracted with 3×20 mL CH2Cl2. The combined organic layers were dried (Na2SO4), concentrated, and the residue was purified by flash chromatography on silica gel (2×15 cm, ethyl acetate-methanol 10:1, 15 mL fractions). Fractions 10-20 provided 144 mg of the desired product (82% yield) as a white solid. evacuated The Schlenk tube was sealed to reach room temperature extracted with 3×20 mL CH2Cl2 The combined organic layers were dried (Na2SO4) concentrated the residue was purified by flash chromatography on silica gel (2×15 cm, ethyl acetate-methanol 10:1, 15 mL fractions)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2,3,5,6-Tetrahydro-1H-benzo[b][1,5]diazocin-4-one (prepared as in J. Am. Chem. Soc. 2004, 126, 3529-3533) (1.00 g, 5.68 mmol) was dissolved in anh acetonitrile (50 ml). Acetic anhydride (587 μL, 6.25 mmol) was added and the reaction mixture was heated to 80° C. for 16 h. The reaction mixture was concentrated, triturated with ether, and filtered to afford title compound as a beige solid. (1.063 g, 86%) mp 236-239° C.; LCMS: m/z=219.30 (M+H+), HPLC (95% purity); 1H NMR (400 MHz, DMSO-d6) δ 7.82 (m, 1H), 7.38 (m, 4H), 4.64 (m, 1H), 4.29 (m, 1H), 3.87 (m, 1H), 2.92 (m, 1H), 2.57 (m, 1H), 2.26 (m, 1H), 1.69 (s, 3H). The reaction mixture was concentrated triturated with ether filtered

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A Schlenk tube was charged with CuI (9.6 mg, 0.050 mmol, 5.0 mol %), 2-azetidinone (86 mg, 1.21 mmol), K3PO4 (430 mg, 2.03 mmol), evacuated, and backfilled with Ar. N,N′-Dimethylethylenediamine (11 μL, 0.103 mmol, 10 mol %), 2-iodobenzylamine (132 μL, 1.00 mmol), and toluene (1 mL) were added under Ar. The Schlenk tube was sealed and the reaction mixture was stirred at 100° C. for 22 h. The resulting suspension was allowed to reach room temperature, poured into a solution of 30% aq ammonia (1 mL) in water (20 mL), and extracted with 3×20 mL CH2Cl2. The combined organic layers were dried (Na2SO4), concentrated, and the residue was purified by flash chromatography on silica gel (2×15 cm, ethyl acetate-methanol 10:1, 15 mL fractions). Fractions 10–20 provided 144 mg of the desired product (82% yield) as a white solid. evacuated The Schlenk tube was sealed to reach room temperature extracted with 3×20 mL CH2Cl2 The combined organic layers were dried (Na2SO4) concentrated the residue was purified by flash chromatography on silica gel (2×15 cm, ethyl acetate-methanol 10:1, 15 mL fractions)