dimethyl 1-benzylpyrrolidine-3,4-dicarboxylate

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

Procedure: To a solution of dimethyl 1-benzylpyrrolidine-3,4-dicarboxylate (0.50 g) in THF (20 mL) was added LiAlH4 (3.0 eq) at 0° C. under N2. The reaction mixture was heated to the room temperature and stirred for 24 h. The reaction was quenched with water, 10% NaOH and water in turn. The mixture was filtered and the filtrate was concentrated in vacuo. The residue was chromatographed with a silica gel column (eluting agent: 10:1 (v/v) CH2Cl2/CH3OH) to give the title compound (0.31 g, 63.79%). The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 222.3 (M+1). The reaction was quenched with water, 10% NaOH and water in turn The mixture was filtered the filtrate was concentrated in vacuo The residue was chromatographed with a silica gel column (eluting agent: 10:1 (v/v) CH2Cl2/CH3OH)

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

Procedure: To a solution of dimethyl maleate (4.00 g) in CH2Cl2 (100 mL) was added N-(methoxymethyl)-N-(trimethylsilylmethyl)benzylamine (1.2 eq) followed by a solution of TFA in CH2Cl2 (0.1 eq, 1 M) dropwise at 0° C. under N2. The reaction mixture was heated to room temperature and stirred for 6 h, washed with water followed by brine. The mixture was dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was chromatographed with a silica gel column (eluting agent: 3:1 (v/v) PE/EA) to yield the title compound (6.62 g, 86.02%). The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 278 (M+1); 1H NMR (400 MHz, CDCl3) δ: 2.70-2.75 (m, 2H), 3.12-3.17 (m, 1H), 3.30-3.33 (m, 2H), 3.66 (s, 6H), 7.24-7.31 (m, 5H). washed with water The mixture was dried over anhydrous Na2SO4 concentrated in vacuo The residue was chromatographed with a silica gel column (eluting agent: 3:1 (v/v) PE/EA)

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

Procedure: To a cooled (0° C.) solution of 1-benzyl-pyrrolidine-3,4-dicarboxylic acid dimethyl ester (8.66 g, 31.2 mmol) in THF (40 mL) was added LAH (2 M in THF, 62 mL, 62 mmol) over a ten minute period. The reaction mixture was stirred while warming (rt, 17 h). The reaction mixture was then cooled (0° C.), and stirred (15 min), and slowly treated sequentially with an addition of H2O (2.8 mL), 2 M NaOH (4.3 mL), and H2O (8.5 mL). The reaction mixture was then heated to reflux (64° C., 1 h). The reaction mixture was cooled and filtered through Celite® and the solid was washed with EtOAc. The filtrate was concentrated in vacuo to afford the title compound as a yellow oil (7.89 g, 100%). 1H NMR (500 MHz, CDCl3): 7.38-7.21 (m, 5H), 3.84-3.70 (m, 4H), 3.65-3.59 (m, 2H), 2.70-2.58 (m, 4H), 2.58-2.47 (m, 2H). The reaction mixture was then cooled (0° C.) stirred (15 min) The reaction mixture was then heated to reflux (64° C., 1 h) The reaction mixture was cooled filtered through Celite® the solid was washed with EtOAc The filtrate was concentrated in vacuo

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

Procedure: To a solution of dimethyl 1-benzylpyrrolidine-3,4-dicarboxylate (0.50 g) in THF (20 mL) was added LiAlH4 (3.0 eq) at 0° C. under N2. The reaction mixture was heated to the room temperature and stirred for 24 h. The reaction was quenched with water, 10% NaOH and water in turn. The mixture was filtered and the filtrate was concentrated in vacuo. The residue was chromatographed with a silica gel column (eluting agent: 10:1 (v/v) CH2Cl2/CH3OH) to give the title compound (0.31 g, 63.79%). The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 222.3 (M+1). The reaction was quenched with water, 10% NaOH and water in turn The mixture was filtered the filtrate was concentrated in vacuo The residue was chromatographed with a silica gel column (eluting agent: 10:1 (v/v) CH2Cl2/CH3OH)

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

Procedure: To a solution of dimethyl maleate (4.00 g) in CH2Cl2 (100 mL) was added N-(methoxymethyl)-N-(trimethylsilylmethyl)benzylamine (1.2 eq) followed by a solution of TFA in CH2Cl2 (0.1 eq, 1 M) dropwise at 0° C. under N2. The reaction mixture was heated to room temperature and stirred for 6 h, washed with water followed by brine. The mixture was dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was chromatographed with a silica gel column (eluting agent: 3:1 (v/v) PE/EA) to yield the title compound (6.62 g, 86.02%). The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 278 (M+1); 1H NMR (400 MHz, CDCl3) δ: 2.70-2.75 (m, 2H), 3.12-3.17 (m, 1H), 3.30-3.33 (m, 2H), 3.66 (s, 6H), 7.24-7.31 (m, 5H). washed with water The mixture was dried over anhydrous Na2SO4 concentrated in vacuo The residue was chromatographed with a silica gel column (eluting agent: 3:1 (v/v) PE/EA)