1-bromobicyclo[2.2.2]octane

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: methyl 2-(benzyloxycarbonylamino)acrylate (2.05 g, 0.0095 mol, 1 eq.), 1-bromobicyclo[2.2.2]octane (1.8 g, 0.0095 mol, 1 eq.) and AIBN (0.312 g, 0.0019 mol, 0.2 eq.) were dissolved in benzene (30 mL) and heated to reflux. Bu3SnH (5.53 g, 0.019 mol, 2 eq.) was then added. The resulting mixture was stirred at reflux for 14 hrs. The solvent was removed and the residue was purified via preparative TLC (EtOAc/Petroleum ether=1:9) to give methyl 2-(benzyloxycarbonylamino)-3-(bicyclo[2.2.2]octan-1-yl)propanoate (480 mg, 15%) as a foam. 1H NMR (CDCl3, 400 MHz) δ 7.35 (m, 5H), 5.13 (m, 2H), 4.42 (m, 1H), 3.73 (s, 3H), 1.8-1.1 (m, 15H), 1.28 (m, 1H). heated to reflux at reflux for 14 hrs The solvent was removed the residue was purified via preparative TLC (EtOAc/Petroleum ether=1:9)

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

Procedure: methyl 2-(benzyloxycarbonylamino)acrylate (2.05 g, 0.0095 mol, 1 eq.), 1-bromobicyclo[2.2.2]octane (1.8 g, 0.0095 mol, 1 eq.) and AIBN (0.312 g, 0.0019 mol, 0.2 eq.) were dissolved in benzene (30 mL) and heated to reflux. Bu3SnH (5.53 g, 0.019 mol, 2 eq.) was then added. The resulting mixture was stirred at reflux for 14 hrs. The solvent was removed and the residue was purified via preparative TLC (EtOAc/Petroleum ether=1:9) to give methyl 2-(benzyloxycarbonylamino)-3-(bicyclo[2.2.2]octan-1-yl)propanoate (480 mg, 15%) as a foam. 1H NMR (CDCl3, 400 MHz) δ 7.35 (m, 5H), 5.13 (m, 2H), 4.42 (m, 1H), 3.73 (s, 3H), 1.8-1.1 (m, 15H), 1.28 (m, 1H). heated to reflux at reflux for 14 hrs The solvent was removed the residue was purified via preparative TLC (EtOAc/Petroleum ether=1:9)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred mixture of 1-methoxybicyclo[2.2.2]octane (4.0 g, 28 mmol) and acetyl bromide (6.2 g, 50.4 mmol) was added 10 drops of stannic chloride at 0° C. After stirring for 0.5 h, the temperature was allowed to rise to 20-25° C. and stirring was continued at the same temperature for 3 h. After cooling to 0° C., water (30 mL) was added and the mixture was stirred for 10 min. Then the mixture was poured into water (150 mL) and extracted with ether (100 mL×3). The ether layers were combined, washed with aqueous sodium bicarbonate and water, and dried over sodium sulfate. The solvent was removed under reduced pressure to produce 1-bromobicyclo[2.2.2]octane (4.0 g, 75%), which was used for next step without purification. 1H NMR (CDCl3) δ 2.23 (m, 6H), 1.95 (m, 1H), 1.81-1.63 (m, 6H), 1.52 (m, 1H). to rise to 20-25° C. stirring was continued at the same temperature for 3 h the mixture was stirred for 10 min extracted with ether (100 mL×3) washed with aqueous sodium bicarbonate and water dried over sodium sulfate The solvent was removed under reduced pressure

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

Procedure: 1-Bromobicyclo[2.2.2]octane (4.6 g, 24.3 mmol), ethyl (Z)-2-hydroxyimino-3-oxobutyrate (3.78 g, 24.3 mmol) and silver trifluoromethanesulphonate (6.32 g, 24.6 mmol) were reacted under similar conditions to that described in Example 31a to give the title compound (1.47 g, 22%); νmax (CH2Cl2) 2950, 2925, 2860, 1735, 1685, 1370 and 1325 cm-1 ; δH (60 MHz, CDCl3) 1.30 (3H, t, J ca 7 Hz), 1.64 (S) and 1.75 (s) (together 13H), 2.36 (3H, s), and 4.30 (2H, q); [Ammonia CI mass spectrum Found MH+ (288)].

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

Procedure: methyl 2-(benzyloxycarbonylamino)acrylate (2.05 g, 0.0095 mol, 1 eq.), 1-bromobicyclo[2.2.2]octane (1.8 g, 0.0095 mol, 1 eq.) and AIBN (0.312 g, 0.0019 mol, 0.2 eq.) were dissolved in benzene (30 mL) and heated to reflux. Bu3SnH (5.53 g, 0.019 mol, 2 eq.) was then added. The resulting mixture was stirred at reflux for 14 hrs. The solvent was removed and the residue was purified via preparative TLC (EtOAc/Petroleum ether=1:9) to give methyl 2-(benzyloxycarbonylamino)-3-(bicyclo[2.2.2]octan-1-yl)propanoate (480 mg, 15%) as a foam. 1H NMR (CDCl3, 400 MHz) δ 7.35 (m, 5H), 5.13 (m, 2H), 4.42 (m, 1H), 3.73 (s, 3H), 1.8-1.1 (m, 15H), 1.28 (m, 1H). heated to reflux at reflux for 14 hrs The solvent was removed the residue was purified via preparative TLC (EtOAc/Petroleum ether=1:9)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred mixture of 1-methoxybicyclo[2.2.2]octane (4.0 g, 28 mmol) and acetyl bromide (6.2 g, 50.4 mmol) was added 10 drops of stannic chloride at 0° C. After stirring for 0.5 h, the temperature was allowed to rise to 20-25° C. and stirring was continued at the same temperature for 3 h. After cooling to 0° C., water (30 mL) was added and the mixture was stirred for 10 min. Then the mixture was poured into water (150 mL) and extracted with ether (100 mL×3). The ether layers were combined, washed with aqueous sodium bicarbonate and water, and dried over sodium sulfate. The solvent was removed under reduced pressure to produce 1-bromobicyclo[2.2.2]octane (4.0 g, 75%), which was used for next step without purification. 1H NMR (CDCl3) δ 2.23 (m, 6H), 1.95 (m, 1H), 1.81-1.63 (m, 6H), 1.52 (m, 1H). to rise to 20-25° C. stirring was continued at the same temperature for 3 h the mixture was stirred for 10 min extracted with ether (100 mL×3) washed with aqueous sodium bicarbonate and water dried over sodium sulfate The solvent was removed under reduced pressure