Lithium Hydroxide → (S)-3-(4-(3,4-Bis(trifluoromethoxy)benzyloxy)phenyl)-3-(isoxazol-3-yl)propanoic acid

Cesium carbonate (137 mg, 0.4 mmol) was added to a mixture of 4-(bromomethyl)-1,2-bis(trifluoromethoxy)benzene 22.1 (71 mg, 0.21 mmol) and 7.5 (82 mg, 0.21 mmol) in DMF (2 mL). The mixture was stirred at room temperature for 16 hours. To the reaction mixture was added LiOH in water (0.5 mL, 1N solution) and THF (1 mL). The mixture was stirred at 23° C. for 3 hours. The mixture was filtered and purified by reverse phase HPLC to give 22 (19 mg) after lyophilization. MS ESI (pos.) m/e 492.1 (M+H). 1H NMR (400 MHz, CDCl3) δ 8.31 (1 H, s), 7.45 (1 H, s), 7.39 (2 H, s), 7.21 (2 H, d, J=8.3 Hz), 6.93 (2 H, d, J=8.8 Hz), 6.08 (1 H, s), 5.05 (2 H, s), 4.57 (1 H, t, J=7.6 Hz), 3.37 (1 H, dd, J=16.6, 7.8 Hz), 3.00 (1 H, dd, J=16.6, 7.8 Hz).

1. stirringThe mixture was stirred at 23° C. for 3 hours
2. filtrationThe mixture was filtered
3. custompurified by reverse phase HPLC

ORD record

ord-976db3060e2e4a8c848f486e08be173b

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08003648B2