Chloride → HCID 25142740, compound

Participants

Reaction Conditions

Reaction Steps

In a manner similar to the method described in example 2 (method B), rac-(1R,2S,6R)-6′-chloro-2-(3-chlorophenyl)-6-ethoxy-spiro[cyclohexane-1,3′-[3H]indole]-2′,4(1′H)-dione (150.0 mg, 0.34 mmole) was reacted with NH2OH—HCl (119.5 mg, 1.72 mmol), NaOH (68.8 mg, 1.72 mmole) in EtOH-water (3/2, 10 mL) at refluxing for 2 hrs, followed by reacting with p-oluenesulfonyl chloride (133.1 mg, 0.70 mmol) in dichloromethane (10 mL) at room temperature for 2 hrs, and heating under microwave irradiation at 90° C. for 20 min. After diluted with AcOEt the mixture was washed with water, dried over Na2SO4 and concentrated. The residue was purified by chiral column chromatography to give (3S,4S,5R)-6′-chloro-5-(3-chlorophenyl)-3-ethoxy-1,1′,2,2′,3,5,6,7-octahydrospiro[4H-azepine-4,3′-[3H]-indole]-2′,7-dione (10.2 mg), (3R,4R,5S)-6′-chloro-5-(3-chlorophenyl)-3-ethoxyl-1,1′,2,2′,3,5,6,7-octahydrospiro[4H-azepine-4,3′-[3H]-indole]-2′,7-dione (10.8 mg), (3S,4R,5S)-6′-chloro-3-(3-chlorophenyl)-5-ethoxy-1,1′,2,2′,3,5,6,7-octahydrospiro[4H-azepine-4,3′-[3H]-indole]-2′,7-dione (3.8 mg) and (3R,4S,5R)-6′-chloro-3-(3-chlorophenyl)-5-ethoxy-1,1′,2,2′,3,5,6,7-octahydrospiro[4H-azepine-4,3′-[3H]-indole]-2′,7-dione (3.6 mg).

Provenance & Evidence