Acetyl chloride → HCID 178473782, compound

Participants

Reaction Steps

4-{1-[3-({[tert-Butyl(dimethyl)silyl]oxy}methyl)-2-fluorophenyl]azetidin-3-yl}piperidine (70 mg) and TEA (73 mg) were mixed with dichloromethane (2 ml), and acetyl chloride (22 mg) was added thereto, followed by stirring at room temperature for 1 hour. To the reaction mixture were added CHCl3 and a 1M aqueous NaOH solution, the organic layer was dried over Na2SO4, and the organic layer was concentrated under reduced pressure. The obtained residue was mixed with THF (2 ml), and a 1M TBAF/THF solution (0.3 ml) was added thereto, followed by stirring at room temperature for 1 hour. To the reaction mixture were added CHCl3 and a saturated aqueous ammonium chloride solution, and the organic layer was dried over Na2SO4. The reaction mixture was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (CHCl3/MeOH). The purified product thus obtained was mixed with DMF, and CDI (65 mg) was added thereto, followed by stirring at room temperature for 3 hours. To the reaction mixture was added guanidine carbonate (140 mg), followed by stirring at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, water was added thereto, and the insoluble matter was collected by filtration. The obtained solid was purified by basic silica gel column chromatography (CHCl3/MeOH). The purified product thus obtained was mixed with EtOH (1 ml), and L-tartaric acid (16 mg) was added thereto, followed by stirring at room temperature for 1 hour. The precipitated solid was collected by filtration to obtain 3-[3-(1-acetylpiperidin-4-yl)azetidin-1-yl]-2-fluorobenzyl carbamimidoylcarbamate L-tartrate (49 mg).

Provenance & Evidence