Ammonium Chloride → HCID 23156813, compound

Participants

Reaction Steps

8.65 ml (8.65 mmol) of a 1 M lithium bis(trimethylsilyl)amide THF solution was added to a mixture consisting of 400 mg (1.24 mmol) of the 7-chloro-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one obtained in Step B of Example 1; 427.2 mg (3.708 mmol) of 4-piperidinemethanol; 29.2 mg (0.074 mmol) of 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl; and 28.3 mg (0.0309 mmol) of tris(dibenzylideneacetone)dipalladium. The obtained mixture was stirred under heating to reflux over a day and a night. Thereafter, the reaction solution was cooled to a room temperature, and a saturated ammonium chloride aqueous solution was then added thereto, followed by extraction with methylene chloride. Thereafter, the extract was washed with a saturated saline solution, and was then dried over anhydrous sodium sulfate. The extract was concentrated, and the obtained residue was then purified by silica gel column chromatography (methylene chloride:methanol=25:1 to 20:1), so as to obtain 355.6 mg (71%) of 7-(4-hydroxymethylpiperidin-1-yl)-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one in the form of a brown solid.

Provenance & Evidence