methyl (3S,4R)-4-(3-bromophenyl)pyrrolidine-3-carboxylate

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

Procedure: Add a saturated aqueous solution of sodium bicarbonate (350 mL) to a solution of trans-4-(3-bromo-phenyl)-pyrrolidine-3-carboxylic acid methyl ester (11 g, 38 mmol) in methylene chloride (350 mL). Cool the mixture to 0° C. and add BOC-anhydride (8.9 g, 41 mmol) dropwise. Slowly warm the mixture to room temperature and stir for 12 h. Extract the reaction mixture with methylene chloride, dry the combined organic phase over anhydrous sodium sulfate and concentrate under reduced pressure. Purify the residue by silica gel chromatography to provide 13 g of trans-4-(3-bromo-phenyl)-pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester. Slowly warm the mixture to room temperature Extract the reaction mixture with methylene chloride dry the combined organic phase over anhydrous sodium sulfate concentrate under reduced pressure Purify the residue by silica gel chromatography

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

Procedure: Add palladium hydroxide (3.1 g, 22 mmol) to a solution of trans-1-benzyl-4-(3-bromo-phenyl)-pyrrolidine-3-carboxylic acid methyl ester (15 g, 40 mmol) in MeOH (200 mL). Place the mixture under an atmosphere of hydrogen and stir at room temperature for 12 h. Filter the reaction mixture through a pad of diatomaceous earth and concentrate under reduced pressure to provide 11 g (97%) of trans-4-(3-bromo-phenyl)-pyrrolidine-3-carboxylic acid methyl ester. Filter the reaction mixture through a pad of diatomaceous earth concentrate under reduced pressure