反应详情

To a solution of methyl 1-{2-[3-(2-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,3-thiazol-5-yl)-5-fluoro-2-(methyloxy)phenyl]ethyl}-3-azetidinecarboxylate (D82) (100 mg) in isopropanol (15 mL) and water (5 mL) stirred under nitrogen at room temperature was added 2 M NaOH (0.193 mL) in one charge. The reaction mixture was stirred at room temperature overnight. Isopropanol was removed in vacuo. The residue was dissolved in water and acidified with 1N HCl to pH=5. The solvent was removed in vacuo, the residue was dissolved in THF, and filtered. The filtrate was purified by Mass Directed AutoPrep to give 1-{2-[3-(2-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,3-thiazol-5-yl)-5-fluoro-2-(methyloxy)phenyl]ethyl}-3-azetidinecarboxylic acid (E33) (21 mg) as a TFA salt. δH (DMSO-d6, 400 MHz): 1.34 (6H, d), 2.90 (2H, t), 3.47 (2H, br. s.), 3.66 (4H, m), 4.28 (4H, m), 4.80 (1H, m), 7.26 (1H, d), 7.32 (1H, d), 7.73 (1H, dd), 7.90 (1H, dd), 8.01 (1H, d), 8.46 (1H, s), 10.12 (1H, br s), 13.13 (1H, br s). δF (DMSO-d6, 376 MHz): −117.4, −73.9. MS (ES): C25H26ClFN2O4S requires 504. found 505.2 (M+H+).

1. additioncharge
2. customIsopropanol was removed in vacuo
3. dissolutionThe residue was dissolved in water
4. customThe solvent was removed in vacuo
5. dissolutionthe residue was dissolved in THF
6. filtrationfiltered
7. customThe filtrate was purified by Mass Directed AutoPrep