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0 °C

To a solution of isopropyl 4-imidazolecarboxylate (601 mg, 3.9 mmol) in THF (30 mL) is added 6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol (CAS#35550-94-8, 487 mg, 3.0 mmol), which can be prepared as described in Ollivier, R.; et al. Journal of Medicinal Chemistry, 1997, 40, 952-960, followed by triphenylphosphine (1.02 g, 3.9 mmol). The reaction is cooled to 0° C. and diisopropyl azodicarboxylate (755 μL, 3.9 mmol) is added. The reaction is permitted to warm to room temperature and stirred until LC-MS analysis indicates complete consumption of 6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol. The reaction mixture is diluted with saturated aqueous NaHCO3 and ethyl acetate. The layers are separated and the organic layer is dried with Na2SO4, filtered, and concentrated. The resulting residue is purified by silica gel flash chromatography (ethyl acetate-dichloromethane, 0:1 to 1:1) to provide 3-(6,7,8,9-tetrahydro-5H-benzocyclohepten-5-yl)-3H-imidazole-4-carboxylic acid isopropyl ester; HRMS: (ESI) m/z 299.1775 [(M+H)+; calcd for C18H23N2O2: 299.1760]; 1H NMR (400 MHz, CDCl3) δ ppm 1.18 (d, J=6.3 Hz, 3 H), 1.23 (d, J=6.3 Hz, 3 H), 1.36-1.50 (m, 1 H), 1.87-2.24 (m, 4 H), 2.37-2.49 (m, 1 H), 2.85-2.95 (m, 1 H), 2.97-3.09 (m, 1 H), 4.99-5.14 (m, 1 H), 5.94 (d, J=7.8 Hz, 1 H), 6.44 (d, J=10.6 Hz, 1 H), 6.97-7.08 (m, 1 H), 7.08-7.21 (m, 2 H), 7.82-7.93 (m, 2 H). The HCl salt of the title compound can be prepared by dissolution in diethyl ether, followed by treatment with an excess of 1N HCl in diethyl ether. The resulting heterogeneous solution is concentrated to furnish the HCl salt of 3-(6,7,8,9-tetrahydro-5H-benzocyclohepten-5-yl)-3H-imidazole-4-carboxylic acid isopropyl ester.

1. customcan be prepared
2. temperatureto warm to room temperature
3. customconsumption of 6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol
4. additionThe reaction mixture is diluted with saturated aqueous NaHCO3 and ethyl acetate
5. customThe layers are separated
6. dry with materialthe organic layer is dried with Na2SO4
7. filtrationfiltered
8. concentrationconcentrated
9. customThe resulting residue is purified by silica gel flash chromatography (ethyl acetate-dichloromethane, 0:1 to 1:1)