Triphenylphosphine → HCID 24996337, compound

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence