(3aR,4S,7R,7aS) 4,7-Methano-1H-isoindo...

In an autoclave, 3.8 kg of palladium on carbon (10percent w/w 50percent H20) and imide 7 (68.8 kg, 421.3 mol) are suspended in methanol (1000 1). The autoclave isthen closed and inertized with nitrogen, and hydrogen (8 atm) is introduced. The reaction is monitored by hydrogen consumption and by GC. When the reaction is complete, the solution is concentrated to a small volume, and water (200 ml) is added to the resulting suspension in about half an hour. The suspension is then cooled, and the white solid is centrifuged and washed with 50 1 of water to obtain imide 5 (dry weight 63.6 kg, yield 9 1.4percent, purity [GC] 99.99percent).Add compound 4 (3.00 g, 6.00 mmol) and acetonitrile 32 mL to a 100 mL three-neck reaction flask and stir.Then continue to add compound 5 (1.49g, 9.00mmol) to the system.Potassium carbonate (1.24 g, 9.00 mmol), Continue to stir and heat to reflux (T= 145~148°C). Maintain the reflux temperature reaction, The TLC monitors the reaction completely.The solvent was removed by concentration under reduced pressure until no fraction was obtained.To the reduced pressure concentrate, 16 mL of dichloromethane and 32 mL of purified water were added, stirred, and allowed to stand for stratification.Dispense and collect the organic phase.The organic phase was washed twice more with 32 mL of purified water.The organic phase was dried over anhydrous sodium sulfate.Filter by suction and collect the filtrate.The solvent was removed by concentration under reduced pressure.Made a yellow oil.Normal pressure column chromatography (petroleum ether: ethyl acetate = 25:1, 15:1, 5:1) gave 2.The purity is 99.0percent.Take intermediate C (5.0 g, 10.7 mmol), 50 ml of DMF was added and stirred to dissolve. 2 g of molecular sieves, General procedure: To a suspension of corresponding cyclic imide 1a'1k (4mmol), potassium carbonate (4.4mmol) in DMF (5mL), 1-bromo-4-chlorobutane (1, 2-dibromoethane (5 eq) for 2l, 1-bromo-3-chloropropane for 2m, 1-bromo-5-chloropentane for 2n) (4.4mmol) was added dropwise at 0°C. The mixture was stirred at room temperature overnight and then partitioned between ethyl acetate (EA, 20mL) and water (30mL). The organic layer was washed successively with water (3×30mL), saturated brine, and dried over anhydrous Na2SO4. The solvent was evaporated under vacuum and the residue was purified by column chromatography using petroleum ether(PE): EA (8:1) as eluent to give 2a'2n.A mixture of bicyclo[2.2.1]heptane-2, 3-di-exo-carboximide (prepared as described in Chem. Pharm. Bull., 1991 p 2288; 1.0 g, 6.05 mmol), ethyl chloroacetate (1.3 mL, 12.1 mmol), TBAB (39 mg, 0.12 mmol) and potassium carbonate (1.17 g, 8.48 mmol) were irradiated in microwawe for 10 min at 150 C. (150 W). The mixture was then diluted with water and EtOAc. Organic phase was separated, and aqueous phase was extracted with EtOAc (3×15 mL). Combined organic phases were washed with brine (1×15 mL), dried over Na2SO4, filtered and concentrated to afford the title compound as a brown oil (1.74 g, 114%).A mixture of bicyclo[2.2.1]heptane-2, 3-di-exo-carboximide(prepared as described in Chem. Pharm.Bull., 1991 p2288; 1.0 g, 6.05mmol), ethyl chloroacetate (1.3 mL, 12.1 mmol), TBAB (39 mg, 0.12 mmol) andpotassium carbonate (1.17 g, 8.48 mmol) were irradiated in microwave for 10 minat 150C (150W). The mixture was then diluted with water and EtOAc. Organicphase was separated, and aqueous phase was extracted with EtOAc (3x15 mL).Combined organic phases were washed with brine (1x15 mL), dried over Na2SO4, filtered and concentrated to afford the title compound as a brown oil (1.74 g, 114%).

Molecular Weight:165.19
XLogP3:0.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:165.078978594
Monoisotopic Mass:165.078978594
Topological Polar Surface Area:46.2
Heavy Atom Count:12
Complexity:248
Defined Atom Stereocenter Count:4
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes