Hydrochloric Acid → HCID 66877523, compound

Participants

Reaction Conditions

Reaction Steps

To a mixture of cis-[4-(2-amino-4-chloro-phenylamino)-cyclohexyl]-carbamic acid tert-butyl ester (1.25 g, 3.67 mmol, prepared from 1-chloro-4-fluoro-3-nitrobenzene and tert-butyl cis-4-aminocyclohexanecarbamate) and 2-hydroxyisobutyric acid (2.7 g, 25.9 mmol) in water (5 mL) was added concentrated hydrochloric acid (3.25 mL, 40 mmol). The mixture was stirred and heated at 110° C. for 2 days. The dark colored solution was treated with ammonium hydroxide (15 mL, 225 mmol) and extracted with methylene chloride. The organic layer was washed with brine and dried over sodium sulfate. After the evaporation of solvents, a red colored solid was obtained (1.1 g). This material was dissolved in THF (20 mL) and treated with di-tert-butyl-dicarbonate (950 mg, 4.3 mmol). The mixture was stirred at room temperature overnight. Solvents were evaporated and the residue was purified through flash column chromatography using ethyl acetate and hexanes (1:4) to give [4-(5-chloro-2-(1-hydroxy-1-methyl-ethyl)-benzoimidazol-1-yl)-cyclohexyl]-carbamic acid tert-butyl ester (600 mg). This compound was dissolved in methylene chloride (4 mL) and trifluoroacetic acid (1 mL) was added. The solution was stirred at room temperature for 1 hr. Solvents were evaporated and the residue was extracted with methylene chloride and sodium hydroxide solution (1N). The organic layer was dried over sodium sulfate and solvents were evaporated. The residue was dissolved in methylene chloride and treated with hydrogen chloride in dioxane (4M). Solvents were evaporated and the residue was triturated with ether. The purple solid was filtered to give a hydrochloride salt of cis-2-[1-(4-amino-cyclohexyl)-5-chloro-1H-benzoimidazol-2-yl]-propan-2-ol. 1H-NMR (CD3OD) □ 7.96 (d, 1H), 7.57 (s, 1H), 7.21 (d, 1H), 5.34 (m, 1H), 2.61 (m, 2H), 1.72-1.89 (m, 13H).

Provenance & Evidence