4-Fluorophenol → HCID 86644307, compound

Participants

Reaction Steps

To a solution of the 2-methyl-8-(pyridazin-3-yl)-2,3,4,5-tetrahydro-1H-benzo[c]azepin-5-ol (170 mg, 0.67) from Step H above in THF (5 mL) was added 4-fluorophenol (98 mg, 0.87 mmol), tributylphosophine (176 mg, 0.52 mmol) and 1,1′-(azodicarboyl)dipiperidine (220 mg, 0.87 mmol) at room temperature. The reaction mixture was stirred at room temperature for 3 hours. The mixture was diluted with dichloromethane and washed with water, brine, dried over sodium sulfate and concentrated. The residue was purified by chromatography (98:2 to 95:5 ethyl acetate/methanol), followed by preparative HPLC to give 544-fluorophenoxy)-2-methyl-8-(pyridazin-3-yl)-2,3,4,5-tetrahydro-1H-benzo[c]azepine (120 mg, 51%) as a gum-like solid. This compound was resolved using Chiralcel OJ column (eluente:80 Hep:20 EtOH:0.1 DEA) to give (+)-enantiomer (36 mg)) and (−)-enantiomer (37 mg).

Provenance & Evidence