Thionyl Chloride → HCID 178471775, 화합물

참여 물질

반응 단계

A solution of ethyl [trans-4-({ethyl[2-(hydroxymethyl)-4-(trifluoromethyl)phenyl]amino}methyl)cyclohexyl]acetate (Step B; 60 mg; 0.149 mmol) in toluene (1 mL) was added dropwise to a stirred solution of thionyl chloride (12.3 μL; 0.169 mmol) in toluene (300 μL) at 0° C. The reaction stirred at room temperature for 1.5 h. Pyridine (27 mL) was added and the reaction was partitioned between toluene (10 mL) and H2O (10 mL). The aqueous layer was re-extracted with toluene (10 mL) and the combined organic layers were washed with brine (10 mL), dried (Na2SO4), filtered and concentrated in vacuo. The residue was dissolved in DMF (1 mL) and (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one (intermediate 17; 56 mg; 0.179 mmol) and potassium tert-butoxide (23.5 mg; 0.209 mmol) were added successively. The reaction stirred for 72 h and was quenched with sat. NH4Cl. The reaction was partitioned between sat. NH4Cl (10 mL) and EtOAc (10 mL). The aqueous layer was re-extracted with EtOAc (3×10 mL) and the combined organic layers were washed with brine (10 mL), dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by flash silica gel chromatography (0-20% EtOAc/hexanes gradient) and chiral HPLC (1.5% IPA/heptane; ChiralPak IA column) to afford ethyl (trans-4-{[[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4-(trifluoromethyl)phenyl](ethyl)amino]methyl}cyclohexyl)acetate as a clear glass. LCMS=697.3 (M+1)+. 1H NMR (CDCl3, 500 MHz): δ 7.92 (s, 1 H), 7.81 (s, 2 H), 7.65 (s, 1 H), 7.58 (d, J=8.4 Hz, 1H), 7.30-7.27 (m, 1 H), 5.78 (d, J=8.1 Hz, 1 H), 4.88 (d, J=16.5 Hz, 1 H), 4.74-4.69 (m, 1 H), 4.11 (q, J=7.1 Hz, 2 H), 3.17-3.10 (m, 2 H), 3.05-2.97 (m, 2 H), 2.15 (d, J=6.8 Hz, 2 H), 1.80-1.68 (m, 4 H), 1.66-1.50 (m, 1 H), 1.46-1.39 (m, 1 H), 1.25 (t, J=7.1 Hz, 3 H), 1.07 (t, J=7.0 Hz, 3 H), 1.03-0.85 (m, 4H), 0.71 (d, J=6.6 Hz, 3 H).

출처 및 근거