C(N(CC)CC)C.Cl.[F:9][C:10]1[CH:15]=[CH:14][C:13]([S:16]([CH2:19][CH:20]2[CH2:23][NH:22][CH2:21]2)(=[O:18])=[O:17])=[CH:12][CH:11]=1.[F:24][C:25]1[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:26]=1[CH:32]1[CH2:34][O:33]1.Cl([O-])(=O)(=O)=O.[Li+]>C(#N)C.O>[F:24][C:25]1[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:26]=1[CH:32]([OH:33])[CH2:34][N:22]1[CH2:23][CH:20]([CH2:19][S:16]([C:13]2[CH:14]=[CH:15][C:10]([F:9])=[CH:11][CH:12]=2)(=[O:18])=[O:17])[CH2:21]1Triethylamine (210 μL, 1.52 mmol) was added to a stirred suspension of 3-{[(4-fluorophenyl)sulfonyl]methyl}azetidine hydrochloride (Example 1 Step 4, 270 mg, 1.02 mmol) in acetonitrile (3 mL) under nitrogen. 2-(2,4-Difluorophenyl)oxirane (WO 99/23083; 1:1 mixture of enantiomers, 238 mg, 1.52 mmol) was added followed by lithium perchlorate (110 mg, 1.03 mmol). The resulting solution was stirred overnight at room temperature. The reaction mixture was poured into water and extracted with dichloromethane (x3). The combined organic layers were washed with water (x3) and brine, dried over MgSO4 and evaporated in vacuo. The residue was triturated with diethyl ether/isohexane then with 5% methanol/ethyl acetate to give 1-(2,4-difluorophenyl)-2-(3-{[(4-fluorophenyl)sulfonyl]methyl}azetidin-1-yl)ethanol (134 mg, 34%). 1H NMR (500 MHz, CD3OD) δ 7.96–7.92 (2H, m), 7.50–7.46 (1H, m), 7.39–7.33 (2H, m), 6.93–6.91 (1H, m), 6.88–6.84 (1H, m), 3.48 (2H, d, J=7.3 Hz), 3.44–3.38 (2H, m), 2.96–2.88 (2H, m), 2.83–2.75 (1H, m), 2.67–2.61 (2H, m); m/z (ES+) 386 (M+H)+.
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