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A suspension of zinc powder (5.59 g, 85.5 mmol) in tetrahydrofuran (THF, 100 mL) at 0° C., was treated with titanium(IV)chloride (4.69 mL, 42.8 mmol) by dropwise addition. The resultant mixture was heated at reflux for 2 h. The resultant solution was cooled to 0° C. 3-oxo-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester (2.4 g, 10.7 mmol) and 5-bromo-9-oxo-9H-xanthene-3-carboxylic acid diethylamide (4.0 g, 10.7 mmol) were added and the solution was heated at reflux for 4 h. Potassium sodium tartrate tetrahydrate (30 g, 106 mmol) was added to the reaction mixture and allowed to stir at ambient temperature overnight. The inorganic solids were removed by filtration and washed successively with THF, EtOAc and dichloromethane. The solvent was evaporated in vacuo. Purification by flash chromatography using a gradient 1% to 10% methanol (with ammonia, 2 N) in dichloromethane as the eluent gave Compound 7j (3.65 g). Crude product was purified by reverse phase preparative HPLC, using a gradient of acetonitrile (10% to 90%) in water with trifluoroacetic acid (0.1%), to give the trifluoroacetic acid salt of compound 7j. MS: m/z 467.0 (MH+). 1H NMR (DMSO-d6): δ 1.0-1.2 (br m, 6H), 1.32 (d, 2H, J=7.9 Hz), 1.75-1.85 (br m, 2H), 2.85-3.10 (m, 4H), 3.15-3.50 (br m, 4H), 4.01 br s, 2H), 7.15-7.26 (m, 3H), 7.42 (d, 1H, J=6.7 Hz), 7.49 (d, 1H, J=7.9 Hz), 7.66 (d, 1H, J=7.9 Hz), 8.81 (br s, 1H) and 9.12 br d, 1H).

1. temperatureat reflux for 2 h
2. temperaturethe solution was heated
3. temperatureat reflux for 4 h
4. customThe inorganic solids were removed by filtration
5. washwashed successively with THF, EtOAc and dichloromethane
6. customThe solvent was evaporated in vacuo
7. customPurification by flash chromatography