Lithium Hydroxide → 2-(4-(4-(5-(2-Methyl-5-(trifluoromethyl)oxazole-4-carboxamido)pyridin-2-yl)phenyl)-2-oxabicyclo[2.2.2]octan-1-yl)acetic acid

Participants

Reaction Steps

To a solution of methyl 2-(4-(4-(5-aminopyridin-2-yl)phenyl)-2-oxabicyclo[2.2.2]octan-1-yl)acetate (212 mg, 0.602 mmol) in DMF (3 ml) at rt under N2 was added 2-methyl-5-(trifluoromethyl)oxazole-4-carboxylic acid (141 mg, 0.722 mmol) and Et3N (0.167 ml, 1.203 mmol. The mixture was stirred for 5 minutes before the addition of HATU (274 mg, 0.722 mmol) at room temperature. Upon completion of reaction, the mixture was diluted with H2O (25 ml) and extracted with EtOAc (50 ml). The organic portion was washed with brine, dried over sodium sulfate, filtered and concentrated to afford the crude methyl ester. LC/MS, ESI-MS (+): 530.0, RT: 1.37 (Condition E). The crude methylester was suspended in THF (4 ml) and treated with 1N LiOH (0.722 ml, 0.722 mmol). Upon completion of reaction, the mixture was diluted with H2O and brought to pH 5 with acetic acid. The resulting slurry was filtered, washed with H2O and dried at 80° C. for several hours. The crude solid was triturated with hot EtOH, AcN, and Et2O to give the title compound as off-white solid after drying (65 mg, 19% yield). HR/MS (M+H)+ found 516.1749. calc. 516.1735, RT: 2.76 (Condition L). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.08 1 (s, 1H), 10.92 (s, 1H), 9.03 (s, 1H), 8.30 (d, J=8.0 Hz, 1H), 7.99 (d, J=16.0 Hz, 2H), 7.94 (d, J=16.0 Hz, 1H), 7.44 (d, J=8.00 Hz, 2H), 3.91 (s, 2H), 2.63 (s, 3H), 2.33 (s, 2H), 2.08-1.85 (m, 8H).

Provenance & Evidence