Lithium Hydroxide → HCID 86618627, compound

Participants

Reaction Conditions

Reaction Steps

cis-4-Amino-1-cyclohexanecarboxylic acid (1.5 g, 10.5 mmol) was suspended in THF (40 mL), lithium hydroxide (1N aqueous solution, 10.5 mL, 10.5 mmol) was added, followed by benzoylisothiocyanate (1.42 mL, 10.5 mmol). The mixture was stirred for 30 min, lithium hydroxide (1N aqueous solution, 10.5 mL, 10.5 mmol) was added, and the mixture was heated to reflux for 1 h. Additional lithium hydroxide (1N aqueous solution, 0.3 mL, 0.3 mmol) was added, heating was continued for 30 min, and then the mixture was cooled to 25° C. 2-Bromo-1-(4-cyanophenyl)-ethanone (2.35 g, 10.5 mmol) was added, the mixture was heated to reflux for 1 h, and then concentrated. The crude product was chromatographed with 25% acetone in hexane with 0.5% acetic acid. Further chromatography with 20% acetone:20% ethyl acetate:60% hexane provided the intermediate 4-[4-(4-cyano-phenyl)-thiazol-2-ylamino]-cyclohexanecarboxylic acid (0.196 g, 0.609) that was dissolved in dioxane (30 mL). Carbonyl diimidazole (118 mg, 0.73 mmol) was added and the mixture was heated to 100° C. for 16 h. The mixture was concentrated and flashed with 10% acetone in hexane to give 105 mg of 4-[2-(3-oxo-2-azabicyclo[2.2.2]oct-2-yl)-1,3-thiazol-4-yl]benzonitrile.

Provenance & Evidence