methyl 1-benzyl-4-phenylpyrrolidine-3-carboxylate

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

Procedure: A solution of 2.61 g (8.8 mmol) of 1-phenylmethyl-3-(SR)-carbomethoxy-4-(SR)-phenylpyrrolidine (from Example 1, Step A) in 100 mL of THF at -78 ° C. was treated with 9.2 mL of 1.5 M diisobutyl-aluminum hydride solution in toluene. The reaction was warmed to 0 ° C. and stirred for 1 h. The reaction was quenched with 50 mL of sat'd sodium potassium tartrate solution, diluted with 100 mL of ether and stirred at rt for 20 h. The layers were separated and the organic layer was washed with 75 mL of H2O, dried over MgSO4 and concentrated in vacuo. Flash chromatography on 100 g of silica gel using 1:1 v/v, then 3:2 v/v EtOAc/hexanes as the eluant afforded 1.99 g (84%) of the title compound as a solid. 1H NMR (500 MHz, CDCl3): δ2.56-2.63 (m, 1H), 2.80 (dd, J=4.3, 9.4, 1H), 2.91-2.98 (m, 2H), 3.05 (dd, J=6.9, 9.6, 1H), 3.27 (dd, J=5.0, 10.7, 1H), 3.44 (dd, J=5.5, 10.8, 1H), 3.62 (q, J=9.0, 1H), 3.76 (ABq, J=24.2, 2H), 7.22-7.40 (10H). Mass Spectrum (NH3 -CI): m/z 268 (M+1). The reaction was quenched with 50 mL of sat'd sodium potassium tartrate solution diluted with 100 mL of ether stirred at rt for 20 h The layers were separated the organic layer was washed with 75 mL of H2O dried over MgSO4 concentrated in vacuo

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

Procedure: A solution of 1.98 g (12.2 mmol) of methyl (Z)-cinnamate and 5.80 g (24.4 mmol) N-(methoxymethyl)-N-(trimethylsilylmethyl)-benzylamine in 30 mL of CH2Cl2 at 0° C. was treated with 20 drops of trifluoroacetic acid and stirred cold for 1 h. The reaction mixture was partitioned between 200 mL of ether and 100 mL of sat'd NaHCO3 and the layers were separated. The organic layer was washed with 100 mL of sat'd NaCl, dried over MgSO4 and concentrated in vacuo. Flash chromatography on 150 g of silica gel using 20:1 v/v CH2Cl2/ether as the eluant afforded 2.61 g (72%) of the title compound as an oil. 1H NMR (500 MHz, CDCl3): δ2.83 (t, J=8.7, 1H), 3.09-3.19 (m, 6H), 3.16 (s, 3H), 3.46-3.51 (m, 1H), 3.73-3.79 (m, 3H), 7.19-7.42 (1OH). Mass Spectrum (NH3 -CI): m/z 296 (M+1). The reaction mixture was partitioned between 200 mL of ether and 100 mL of sat'd NaHCO3 the layers were separated The organic layer was washed with 100 mL of sat'd NaCl dried over MgSO4 concentrated in vacuo