Diisopropylethylamine → 1-(3-(4-(5-(3,5-Dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydrofuran-3-yl)phenyl)-3-fluoroazetidin-1-yl)-2-(methylsulfonyl)ethanone

Participants

Reaction Steps

To a stirred solution of 3-(4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydrofuran-3-yl)phenyl)-3-fluoroazetidine hydrochloride (Example 1, Intermediate 3) (0.25 g, 0.535 mmol) in THF (5 mL) was added DIPEA (0.933 mL, 5.35 mmol) at room temperature and stirred for 10 minutes at room temperature. Methane sulfonyl acetic acid (0.147 g, 1.07 mmol), T3P (50% solution in ethyl acetate, 1.6 mL, 2.675 mmol) were added at room temperature. Resulting reaction mixture was stirred for 16 hours at room temperature under nitrogen atmosphere. After complete consumption of starting material, reaction mixture was quenched with water (20 mL) and extracted with ethyl acetate (5×25 mL). Combined organic layer was washed with saturated solution of NaHCO3 (2×100 mL), dried over sodium sulphate and concentrated in vacuo to get pale yellow oil (0.32 g, crude). Crude was purified by column chromatography using 100-200 mesh silica gel. Desired product gets eluted in 0.6% MeOH in DCM to afford white semisolid (0.160 g), which was triturated with DCM: n-pentane (1:10; 2×5 mL) to afford product as off white solid. Yield: 0.145 g (49.15%). 1H NMR (400 MHz, DMSO-d6) δ: 3.11 (s, 3H), 3.20 (d, J=17.16 Hz, 1H), 3.65 (d, J=17.12 Hz, 1H), 4.24 (s, 2H), 4.34 (d, J=21.6 Hz, 2H), 4.70 (d, J=21.52 Hz, 2H), 7.27 (d, J=7.96 Hz, 2H), 7.47 (d, J=9.36 Hz, 2H), 7.73 (d, J=3.92 Hz, 3H). LC-MS (m/z): =550.1 (M−H). HPLC purity: 98.75%.

Provenance & Evidence