Acetic Acid → 1-(1-{3-[(R)-1-(4-Chloro-3-methyl-phenyl)-propylamino]-phenyl}-ethyl)-azetidine-3-carboxylic acid

Participants

Reaction Steps

To a solution of INT 11 (213 mg, 0.71 mmol) and azetidine-3-carboxylic acid (75 mg, 0.74 mmol) in MeOH (7 mL) was added HOAc (0.040 mL, 0.71 mmol) followed by NaCNBH3 (44 mg, 0.71 mmol). The reaction mixture was stirred at room temperature for 40 hours. More azetidine-3-carboxylic acid (10 mg, 0.099 mol) and NaCNBH3 (10 mg, 0.16 mmol) were added and the mixture was stirred at room temperature for an additional 4 hours. The mixture was concentrated. The residue was taken up in CH2Cl2 and washed with brine. The aqueous layer was extracted with CH2Cl2 and EtOAc. The combined organic layers were dried over MgSO4, filtered and concentrated. The residue was purified by preparative HPLC (H2O/CH3CN) to afford the title compound Example 6.

Provenance & Evidence