Hydrochloric Acid → HCID 74382623, compound

Participants

Reaction Steps

To a solution of 3-[5-(tert-butyl-dimethyl-silanyloxymethyl)-imidazol-1-yl]-2,2-dimethyl-indan-1-one (1.07 g, 2.9 mmol), which can be prepared as described in Example 21, in ethanol (30 mL) is added pyridine (4.7 mL, 58 mmol) followed by the HCl salt of O-ethyl-hydroxylamine (850 mg, 8.7 mmol). The reaction is then heated at reflux for 1 hour, at which time it is cooled to room temperature and concentrated to near dryness. The resulting residue is diluted with ethyl acetate and washed with saturated aqueous NaHCO3. The organic layer is dried with Na2SO4, filtered, and concentrated. The resulting residue is taken directly to the next step, wherein it is dissolved in THF (30 mL) and then treated with a 1N solution of tetrabutylammonium fluoride in THF (5.0 mL, 5.0 mmol). The reaction is permitted to stir for 1 hour, at which time it is diluted with saturated aqueous NH4Cl and ethyl acetate. The layers are separated and the aqueous layer is extracted an additional two times with ethyl acetate. The combined organic layers are dried with Na2SO4, filtered and concentrated. The resulting residue is purified by silica gel flash chromatography (methanol-dichloromethane, 0:1 to 1:20) to furnish 3-(5-hydroxymethyl-imidazol-1-yl)-2,2-dimethyl-indan-1-one O-ethyl-oxime as a mixture of geometric isomers; HRMS: (ESI) m/z 300.1710 [(M+H)+: Calcd for C17H21N3O2: 300.1712]; ˜1:1.25 isomeric mixture. Major: 1H NMR (400 MHz, CDCl3) δ ppm 1.08 (s, 3 H), 1.32 (t, J=7.1 Hz, 3 H), 1.58 (s, 3 H), 4.20 (q, J=7.0 Hz, 2 H), 4.68-4.82 (m, 2 H), 5.59 (s, 1 H), 6.87-7.00 (m, 2 H), 7.17 (d, J=7.3 Hz, 1 H), 7.34-7.52 (m, 2 H), 7.71-7.79 (m, 1 H), Minor: 1H NMR (400 MHz, CDCl3) δ ppm 0.92 (s, 3 H), 1.38 (t, J=7.1 Hz, 3 H), 1.44 (s, 3 H), 4.27 (q, J=7.1 Hz, 2 H), 4.69-4.82 (m, 2 H), 5.60 (s, 1 H), 6.88-7.01 (m, 2 H), 7.28-7.30 (m, 1 H), 7.34-7.50 (m, 2 H), 8.37-8.45 (m, 1 H).

Provenance & Evidence