Hydrochloric Acid → HCID 9843244, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-amino-3-(4-{1,1-dimethylethyl}oxycarbonyl]-piperazin-1-yl)-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide (1 g, Example 2a) in tetrahydrofuran (23 ml) was added 1M aqueous hydrochloric acid (2.78 ml) and water (10 ml). The solution was cooled to 0° C. and sodium nitrite (1.91 g) added portion-wise, whilst maintaining the internal temperature below 5° C. After stirring at 0-5° C. for 0.5 h, a pre-cooled suspension of copper (I) chloride (10.58 g) and copper (II) chloride in water (20 ml) was added portion-wise to the pale yellow suspension. The mixture was stirred at 0° C. for 0.5 h then at room temperature for 0.5 h. The reaction mixture was poured into a mixture of water and dichloromethane and 1/1:0.88 ammonia/water was added until the aqueous phase was homogeneous. The layers were separated and the aqueous phase extracted twice further with dichloromethane. The combined organic extracts were washed with 1/1:0.88 ammonia/water until the aqueous layer was colourless, dried over sodium sulfate, filtered and concentrated under reduced pressure to yield an oil. Purification by chromatography on silica gel, eluting with 20-35% ethyl acetate/iso-hexane gave the subtitle compound as a solid (0.45 g).

Provenance & Evidence