Reaction Steps
To a CH2Cl2 (6 mL) solution of the title compound of Step A (0.236 g, 0.560 mmol) was added m-CPBA (77 wt %, 0.189 g, 0.840 mmol). After 15 h, 10% Na2S2O5 was added and the solution allowed to stir until the aqueous was KI paper negative and extracted with CH2Cl2 (2×). The combined organic layers were dried and treated with MeOH (10 mL) and 1N NaOH (10 mL). After 15 h, the reaction was partially concentrated to remove the MeOH and acidified with 1M HCl (220 mL) then extracted with EtOAc (2×). The combined organic layers were dried and concentrated. Silica gel chromatography (0-30% EtOAc in hexanes) gave 0.091 g (37% yield) of the title compound. (MS (ESI): mass calcd. for C22H22F3NO5, 437.15; m/z found, 382.1 [M-56]+, 460.1 [M+Na]+. 1H NMR (CDCl3): 7.73 (d, J=7.8 Hz, 1H), 7.55 (t, J=7.5 Hz, 1H), 7.45 (t, J=7.7 Hz, 1H), 7.32 (d, J=7.6 Hz, 1H), 6.99 (d, J=8.2 Hz, 1H), 6.87 (dd, J=8.2, 1.9 Hz, 1H), 6.52 (d, J=1.0 Hz, 1H), 4.97-4.88 (m, 1H), 4.30 (dd, J=9.8, 6.4 Hz, 2H), 4.05 (dd, J=9.9, 3.7 Hz, 2H), 1.45 (s, 9H)) and 0.091 g (39% yield) of 3-(4-Hydroxy-2′-trifluoromethyl-biphenyl-3-yloxy)-azetidine-1-carboxylic acid tert-butyl ester (MS (ESI): mass calcd. for C21H22F3NO4, 409.15; m/z found, 354.1 [M-56]+, 432.1 [M+Na]+. 1H NMR (CDCl3): 8.19 (d, J=8.0 Hz, 1H), 7.78 (d, J=8.2 Hz, 1H), 7.61 (t, J=7.2 Hz, 1H), 7.54 (t, J=7.5 Hz, 1H), 7.32 (d, J=7.5 Hz, 1H), 7.12 (dd, J=8.0, 1.3 Hz, 1H), 6.63 (s, 1H), 5.11-5.00 (m, 1H), 4.36 (dd, J=10.1, 6.4 Hz, 2H), 4.12 (dd, J=10.6, 3.6 Hz, 2H), 1.45 (s, 9H).
