Acetic Acid → HCID 131728645, compound

Participants

Reaction Steps

45 mg (0.13 mmol) of (2R,4R/S)-4-(3-ethyl-4-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)hexanal and 21.4 mg (0.13 mmol) of 5-aminoquinolin-2(1h)-one are dissolved in 20 ml of toluene and the solution is admixed with 0.56 ml (1.86 mmol) of titanium tert-butoxide and 0.11 ml of acetic acid. The reaction mixture is heated at 1000 for 2 hours, cooled, poured into water and stirred vigorously. The suspension is filtered through Celite, the filter bed being rinsed thoroughly with ethyl acetate. The phases of the filtrate are separated and extraction is carried out again with ethyl acetate. The extracts are washed with saturated sodium chloride solution and dried over sodium sulphate and the solvent is removed in vacuo to give 80 mg of (5-{[(2R,4R/S)-4-(3-ethyl-4-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)hexylidene]amino}quinolin-2(1H)-one as a crude product. The imine is dissolved in 4.4 ml of CH2Cl2 and the solution is cooled to −30° C. 1.5 ml (1.5 mmol) of a 1M BBr3 solution in dichloromethane are added slowly dropwise over 15 minutes and the reaction solution is allowed to warm to room temperature over 22 hours. It is poured onto a mixture of saturated NaHCO3 solution and ice. It is extracted repeatedly with ethyl acetate and the extracts are washed with saturated NaCl solution and dried over Na2SO4. Purification by column chromatography on silica gel (hexane/isopropanol 16%) and subsequent preparative thin-layer chromatography on an amine phase (Merck NH2F254, ethyl acetate/triethylamine, 2%) yield 8 mg of the title compound and 6 mg of the corresponding 8R-diastereomer.

Provenance & Evidence