4-Chlorobenzoic Acid → HCID 57345436, compound

Participants

Reaction Steps

4-chlorobenzoic acid (0.527 g, 3.37 mmol) and DIPEA (1.176 mL, 6.73 mmol) were mixed in DCM (20 mL) at 0° C. After stirring for 10 min, TBTU (1.103 g, 3.43 mmol) was added to the reaction mixture. The mixture was stirred at 0° C. for 20 min. The above mixture was added in three portions to a solution of (R)-1-(2-(methylamino)pentyl)-azetidin-3-ol (Compound G2.5) (0.58 g, 3.37 mmol) in DCM (20 mL) within 10 min at 0° C. The mixture was stirred at 0° C. for 2.5 h, then warmed to rt and the mixture was stirred overnight. The mixture was concentrated to dryness. To the residue was added aq KOH (30 mL, 15.00 mmol) and methanol (15 mL)/THF (15 mL). The reaction mixture was stirred at rt for 2.5 h. The mixture was concentrated and extracted with DCM (30 mL×2). The DCM layers were combined, evaporated in vacuo to an oil residue. The crude was purified by preparative HPLC to afford the title compound (0.766 g, 73.2%). Mixture of rotamers:

Provenance & Evidence