反应详情

温度

30 °C

(3-{5-[5-Cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-3-yl}-phenyl)-acetic acid methyl ester (0.988 g, 1.81 mmoles) was dissolved into THF (20 mL) and water (6 mL). To this homogeneous mixture was then added LiOH hydrate (152 mg, 3.62 mmoles). This mix was then stirred at 30° C. for 2 hours. After this period the reaction mixture was acidified to pH˜3 using 1H HCl and was evaporated in vacuo. The resulting residue was extracted with DCM (3×15 mL) and the resulting organic layer was dried over anhydrous Na2SO4 and evaporated in vacuo to yield crude product. The crude product was purified using flash silica chromatography (0-5% MeOH/DCM) to yield (3-{5-[5-cyano-1-(2,4-difluoro-benzyl)-6-oxo-4-trifluoromethyl-1,6-dihydro-pyridin-2-yl]-thiophen-3-yl}-phenyl)-acetic acid (625 mg, 65%) as a yellow solid. 1H-NMR (CDCl3): δ 7.64 (br d, J=1.5 Hz, 1H), 7.41-7.38 (m, 2H), 7.32-7.30 (m, 1H), 7.13-7.06 (m, 1H), 6.90-6.84 (m, 1H), 6.82-6.75 (m, 1H), 6.64 (s, 1H), 5.43 (s, 2H), 3.70 (s, 2H). MS(ES+): 531.1 (M+H).

1. waitAfter this period the reaction mixture was acidified to pH˜3
2. customwas evaporated in vacuo
3. extractionThe resulting residue was extracted with DCM (3×15 mL)
4. dry with materialthe resulting organic layer was dried over anhydrous Na2SO4
5. customevaporated in vacuo
6. customto yield crude product
7. customThe crude product was purified