2-Bromo-1-(4-fluorophenyl)ethan-1-one → 4-[({1-[2-(4-Fluorophenyl)-2-oxoethyl]azetidin-3-yl}methyl)sulfonyl]benzonitrile
Reaction equation
Cl.[NH:2]1[CH2:5][CH:4]([CH2:6][S:7]([C:10]2[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][CH:11]=2)(=[O:9])=[O:8])[CH2:3]1.Br[CH2:19][C:20]([C:22]1[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=1)=[O:21]>>[F:28][C:25]1[CH:26]=[CH:27][C:22]([C:20](=[O:21])[CH2:19][N:2]2[CH2:5][CH:4]([CH2:6][S:7]([C:10]3[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][CH:11]=3)(=[O:9])=[O:8])[CH2:3]2)=[CH:23][CH:24]=1Participants
3
Procedure
Following the procedure of Example 2, 4-[(azetidin-3-ylmethyl)sulfonyl]benzonitrile hydrochloride (75 mg, 0.27 mmol) was reacted with 2-bromo-1-(4-fluorophenyl)ethanone. Crude product was purified on a 10 g bond elute silica cartridge using the personal flash master eluting with 0.5% MeOH/DCM to 2% MeOH/DCM to give the freebase as a pale yellow gum (30 mg, 29%). The freebase was dissolved in 3:1 ether/MeOH (5 ml) and 1.0M hydrogen chloride in ether (89μl) was added. The side of the flask was etched and the salt precipitated and was isolated by filtration and dried under vacuum to give the title compound as a white solid (20 mg). 1H NMR (500 MHz, CDCl3) δ 3.05–3.13 (1H, m), 3.90–3.96 (2H, m), 4.03–4.12 (2H, m), 4.23–4.30 (2H, m), 5.06 (2H, s), 7.44 (2H, t, J=8.8 Hz), 8.01 (2H, dd, J=5.4 & 8.8 Hz), 8.09 (2H, d, J=8.6 Hz), 8.21 (2H, d, J=8.6 Hz), 10.62 (1H, s). m/z (ES+) 373 (M+H)+.